JP7479980B2 - Microfluidic Device - Google Patents

Description

The present invention relates to a microchannel device in which a microchannel is formed inside a porous substrate.

In recent years, the development of microchannel devices that utilize micro-sized fine channels to perform biochemical analysis efficiently (micro-amount, rapid, simple) within a single chip has attracted attention in a wide range of fields. Specifically, they have attracted attention in various fields, including biochemical research, medicine, drug discovery, healthcare, the environment, and food. Among them, paper-based paper microanalysis chips have the advantages of being lighter and less expensive than conventional devices, not requiring a power source, and being easily disposable. For this reason, they are expected to be used in medical activities in developing countries and remote areas where medical facilities are not well-equipped, as well as at disaster sites, and as testing devices at airports and other locations where the spread of infectious diseases must be stopped at the border. In addition, because they are inexpensive and easy to use, they are also attracting attention as healthcare devices that can manage and monitor one's own health condition.

In the early 1990s, photolithography and molds were used to form micron-sized fine flow channels on glass or silicon, and microanalysis chips were developed that could perform sample pretreatment, stirring, mixing, reaction, and detection on a single chip. As a result, it was possible to miniaturize testing systems, perform rapid analysis, and reduce specimens, reagents, and waste liquids. However, while the microchannels created using these photolithography techniques have extremely high precision, their manufacturing costs are very high and they are difficult to incinerate, making them difficult to dispose of. In addition, because additional equipment such as syringe pumps is required to send the test liquid into the channel, their use is limited to well-equipped environments and they have been used mainly in biochemistry research institutions.

In response to these issues, paper microanalysis chips use inexpensive materials such as paper and cloth as a base material, and by utilizing the capillary phenomenon of the material itself, they can drive samples and test solutions, making them low-cost and usable in non-electrical environments. They are also easy to carry (distribute) and dispose of (just burn it). Furthermore, since no maintenance is required for the device, anyone (even ignorant elderly people or children) can easily perform POC (point of care) diagnosis at low cost, anywhere (regardless of location, even in places without power). Therefore, research and development of paper microchannel devices for various infectious diseases, specific diseases, and healthcare (chronic disease management, health management) is currently being conducted at research institutes around the world.

Since microfluidic devices use liquids as specimens or test solutions, the materials that form the channels are required to be highly hydrophobic to prevent the liquid from seeping into the channel walls and to prevent the channel walls from swelling due to water absorption when the device is used in a high humidity environment. "Channel walls" refers to the walls that define the channel through which the liquid flows.
Other properties of the flow path material are preferably high solvent resistance so as not to impede the analysis of specimens or test solutions, and at the same time, high mechanical strength and safety for the human body are also required.

Patent Document 1 proposes a microchannel device using polystyrene as a channel material. Patent Document 2 proposes an example of using UV-curable ink as a channel, and Patent Documents 3 and 4 propose an example of using wax ink as a channel. Materials such as polystyrene, UV-curable ink, and wax ink exhibit high hydrophobicity, and have sufficient mechanical strength and human safety. However, they have low resistance to organic solvents and are easily compatible with solvents such as alcohols, ketones, and esters. As a result, when a specimen or test solution containing an organic solvent is used, there is a problem that the channel wall swells or dissolves, causing blockage or collapse of the channel.
Based on these considerations, the present invention proposes a microchannel device that has high hydrophobicity, high mechanical strength, and safety for the human body, as well as high solvent resistance, and is therefore versatile enough to be used with a wide range of specimens and test solutions.

JP 2015-52584 A Patent No. 5935153 US Patent Application Publication No. 2012/0198684 JP 2015-131257 A

The present invention aims to provide a microchannel device that is highly hydrophobic, has high mechanical strength, is safe for the human body, and has high solvent resistance, making it suitable for a wide range of applications.

According to one aspect of the present invention,
A microchannel device having a channel and a channel wall in a porous substrate,
The flow channel is a porous substrate region sandwiched between the flow channel walls,
A microfluidic device is provided in which the channel walls comprise a cyclic olefin copolymer, which is a copolymer of an alkene and a cyclic olefin.

The present invention can provide a microchannel device with wide applicability that is highly hydrophobic, has high mechanical strength, is safe for the human body, and is resistant to organic solvents.

FIG. 2 is a cross-sectional view of a microchannel device formed by permeating COC-A into a porous substrate S1. FIG. 2 is a configuration diagram of a flow path pattern image forming unit 100. FIG. 2 is a diagram illustrating the configuration of a process cartridge P. 2 is a block diagram showing an outline of a control mode of the flow-path pattern image forming unit 100. FIG. FIG. 1 is a graph showing the temperature dependence of the storage modulus and loss modulus of COC-A and COC-B. 1A to 1C are diagrams showing a flow of forming a microchannel device having a protective layer. 11A to 11C are diagrams showing another flow for forming a microchannel device having a protective layer. 11A to 11C are diagrams showing another flow for forming a microchannel device having a protective layer. FIG. 1 shows a microfluidic device having a protective layer and a cover layer.

Hereinafter, exemplary embodiments of the present invention will be described with reference to the drawings. Note that the following embodiments are merely examples, and the present invention is not limited to the contents of the embodiments. In addition, in each of the following drawings, components that are not necessary for the description of the embodiments are omitted from the drawings.
In the present invention, the flow path walls are formed by infiltrating a material containing a cyclic olefin copolymer in which a cyclic olefin is copolymerized into the porous substrate.
The porous substrate will be described later.

<Cyclic Olefin Copolymer>
The cyclic olefin copolymer (COC) according to the present invention is a copolymer of an alkene (acyclic olefin) and a cyclic compound (cyclic olefin).
The alkene is preferably one having 2 to 12 carbon atoms, more preferably a lower alkene having 2 to 6 carbon atoms (α-olefin, acyclic olefin in a broad sense).
Examples of the alkene include ethylene, propylene, butylene, and the like, with ethylene being preferred.
The alkenes can be used alone or in combination of two or more kinds.

The cyclic olefin preferably has 3 to 17 carbon atoms, more preferably 5 to 12 carbon atoms, and may be either a monocyclic compound or a polycyclic compound.
The cyclic olefin preferably has a crosslinked structure, and examples thereof include norbornene, norbornadiene, tetracyclododecene, dicyclopentadiene, and cyclohexene, with norbornene being preferred.
The cyclic olefin may have one or more substituents, such as alkyl groups such as methyl and ethyl groups.
The cyclic olefins may be used alone or in combination of two or more kinds.

The structures of the alkenes and cyclic olefins contained in cyclic olefin copolymers can be identified by NMR.

The content ratio of the alkene to the cyclic olefin is preferably alkene/cyclic olefin=20/1 to 1/20.
The content ratio of the alkene and the cyclic olefin can be determined by NMR.

<Flow path pattern forming unit>
The overall configuration of the flow path pattern image forming unit will be described with reference to Figures 2, 3 and 4. Figure 2 is a cross-sectional view showing the schematic configuration of the flow path pattern forming unit 100, and each component is shown in a simplified manner. Figure 3 is a schematic cross-sectional view of a process cartridge P. Figure 4 is a block diagram showing the schematic control mode of the main parts of the flow path pattern forming unit 100 in this embodiment.

First, the configuration of the flow path pattern forming unit, the flow path pattern forming process, and each member will be described. Each member involved in the flow path pattern image forming process will be described in the order of the flow path pattern image forming process with reference to Figs.
The flow path pattern image forming unit 100 can accommodate a process cartridge P. The process cartridge P has a photosensitive drum 11 as an image carrier. Around the photosensitive drum 11, a charging roller 12, a developing device 20, and a cleaning member 14 are provided. The charging roller 12 is a roller-shaped charging member for charging the surface of the photosensitive drum 11. The developing device 20 develops the electrostatic latent image formed on the surface of the photosensitive drum 11 with resin particles as a developer. The cleaning member 14 cleans the surface of the photosensitive drum 11. Voltages required for forming the flow path pattern image can be applied by a charging high voltage power supply 71, a developing high voltage power supply 72, and a transfer high voltage power supply 74, and are controlled by a control unit 202 (FIG. 4). In addition, the flow path pattern image forming unit 100 can drive the photosensitive drum 11 of the process cartridge P by a motor M1 (not shown), and drive the developing device 20 of the process cartridge P by a motor M2 (not shown).

When the flow path pattern image formation starts, the photosensitive drum 11 is rotated in the direction of the arrow A in Fig. 3 by the drive of the motor M1, and the charging roller 12 is rotated in the direction of the arrow B in Fig. 3 following the rotation of the photosensitive drum 11. In the embodiment described later, the process speed of the photosensitive drum 11 is set to 150 mm/sec.
The photosensitive drum 11 is constructed by providing a photosensitive material such as OPC, amorphous selenium, amorphous silicon, etc., on a cylindrical drum base made of aluminum, nickel, etc. In the embodiment described later, the outer diameter is 20 mm, and the thickness of the photosensitive material is 13 μm.

The charging roller 12, which is a charging member, can be a single-layer roller made of a conductive shaft body (conductive core metal) and a conductive rubber layer. A voltage is applied to the charging roller 12 by a charging high-voltage power source 71, which is a voltage application unit. Next, the charging roller to which the voltage has been applied is brought into contact with the photosensitive drum 11, and the surface of the photosensitive drum 11 is uniformly charged. A DC (direct current) voltage is applied to the charging roller 12, and the surface of the photosensitive drum 11 is uniformly charged to a charging potential Vd by discharging. In the examples described later, a single-layer roller with an outer diameter of 7.5 mm and a volume resistance of 10 ³ to 10 ⁶ Ω·cm is used as the charging roller 12, and a DC voltage is applied. The surface of the photosensitive drum is uniformly charged to −460 V (Vd: dark potential).

After the surface of the photosensitive drum 11 is charged by the charging roller 12, the surface of the photosensitive drum 11 is irradiated with laser light 9 from the exposure unit 73. The surface potential of the photosensitive drum 11 irradiated with the laser light 9 changes to Vl, which is the light area potential, and an electrostatic latent image is formed. In the embodiment described later, Vl is set to -100V. As shown in FIG. 4, the exposure unit 73 receives a time-series electric digital pixel signal of the flow path pattern image information that is input from the controller 200 to the control unit 202 via the interface 201 and has been subjected to flow path pattern image processing. The exposure unit 73 has a laser output unit that outputs the laser light 9 modulated in response to the input time-series electric digital pixel signal, a rotating polygon mirror, an fθ lens, a reflecting mirror, etc., and exposes the surface of the photosensitive drum 11 in the main scanning direction with the laser light 9. An electrostatic latent image corresponding to the flow path pattern image information is formed by this main scanning exposure and the sub-scanning caused by the rotation of the photosensitive drum 11.

<Flow Channel Pattern Image Forming Process>
The flow path pattern image forming unit 100 has a contact/separation unit 75 that controls the position of the developing device 20, and can control the position of the developing device 20 to be different when forming a flow path pattern image and when forming a non-flow path pattern image. The operation of the contact/separation unit 75 is controlled by the control unit 202 shown in FIG.
After the photosensitive drum 11 starts to rotate, the developing device 20 moves the developing roller 23 serving as a developer carrier, which has been spaced apart from the photosensitive drum 11 , by the contact/separation unit 75 so that the developing roller 23 comes into contact with the photosensitive drum 11 .

Next, the developing roller 23 starts to rotate in the direction of the arrow C in FIG. 3, and the supply roller 24 as a supply member starts to rotate in the direction of the arrow D in FIG. 3 by the driving of the motor M2 connected to each. Then, a voltage of -300V is applied to the developing roller 23 from the high-voltage development power supply 72 for the developing roller 23 as a developing voltage. Then, the electrostatic latent image formed on the photosensitive drum 11, that is, the above-mentioned Vl portion, is supplied with developer (particles containing COC) by the developing roller 23 to be developed. The ratio of the moving speed of the surface of the photosensitive drum 11 to the moving speed of the surface of the developing roller 23 at this time (moving speed of the surface of the developing roller 23 / moving speed of the surface of the photosensitive drum 11) is called the developing peripheral speed ratio. By controlling this developing peripheral speed ratio, the amount of developer developed on the photosensitive drum 11 can be controlled. For example, if the development peripheral speed ratio is 2.5, when all the developer on the development roller 23 is developed onto the photosensitive drum 11, the amount of developer per unit area on the surface of the photosensitive drum 11 will be 2.5 times the amount of developer per unit area on the surface of the development roller 23. In this embodiment, the development peripheral speed ratio is controlled by the speed of the motor M2 so that an amount of developer suitable for forming a microchannel wall inside the porous substrate S1 can be developed.

The developed developer image is transferred to a porous substrate S1 as a recording medium by a potential difference with a transfer roller 4 to which a transfer voltage is applied by a transfer high-voltage power supply 74. The porous substrate S1 is a sheet-like medium made of porous material, as described later.
In the examples described later, a roller having an elastic layer of semiconductive sponge, the main component of which is an elastic body, NBR hydrin rubber, and resistance adjusted using an ionic conductive material, on a conductive core metal was used as the transfer roller 4. The outer diameter of the transfer roller 4 was 12.5 mm, and the outer diameter of the conductive core metal was 6 mm. The resistance value of the transfer roller used in the examples was as follows when +2000 V was applied.
Under normal temperature and humidity conditions of 23°C and 50% relative humidity: 1.0 x 10 ⁸ Ω to 3.0 x 10 ⁸ Ω
Under high temperature and humidity environment of 32°C and 80% relative humidity: 0.5 x 10 ⁸ Ω
Under low temperature and low humidity environment of temperature 15° C./relative humidity 10%: 8.0×10 ⁸ Ω

The porous substrate S1 onto which the developer image has been transferred is discharged to the outside of the flow path pattern image forming unit with the developer image facing upward in the direction of gravity. After passing through the transfer roller 4, the photosensitive drum 11 has the untransferred developer scraped off by the cleaning member 14 that is in contact with it. After that, the process from charging by the charging roller 12 is repeated again, thereby continuously forming images.

After the flow path pattern image formation is completed, the developing roller 23 is separated from the photosensitive drum 11 by the contact/separation means 75, and a post-rotation operation is performed to reset the state inside the flow path pattern image forming unit 100, so that the next time flow path pattern image formation is performed, printing can be performed quickly. After the developing roller 23 is separated from the photosensitive drum 11 by the contact/separation means 75, the drive of the motor M2 is turned off to suppress deterioration of the developer.

Next, the operation control of the flow path pattern image forming unit 100 will be described with reference to FIG. 4. The control unit 202 is a means for controlling the operation of the flow path pattern image forming unit 100, and transmits and receives various electrical information signals. It also processes electrical information signals input from various process devices and sensors, and processes command signals to various process devices. The controller 200 transmits and receives various electrical information with the host device. The controller 200 also controls the flow path pattern image forming operation of the flow path pattern image forming unit 100 in accordance with a predetermined control program and reference table via the interface 201 using the control unit 202. The control unit 202 is configured with a CPU 155, which is a central element for performing various arithmetic processing, a memory 15 such as a ROM and a RAM, which are storage elements, and the like. The RAM stores the detection results of the sensors, the count results of the counters, the results of calculations, and the like, and the ROM stores the control program, a data table obtained in advance by experiments, and the like. The control unit 202 is connected to each control target, sensor, counter, and the like in the flow path pattern image forming unit 100. The control unit 202 controls the transmission and reception of various electrical information signals and the timing of driving each unit, and controls the predetermined flow path pattern image formation sequence, etc. For example, it controls the charging high voltage power supply 71, the developing high voltage power supply 72, the exposure unit 73, the transfer high voltage power supply 74, the developing peripheral speed change means 76, etc., and adjusts the applied voltage, the exposure amount, etc.

In the flow path pattern image forming unit 100 in FIG. 2, the connection from the control unit 202 to the charging high voltage power supply 71, the developing high voltage power supply 72, the exposure unit 73, and the transfer high voltage power supply 74 is not shown. However, in reality, the charging high voltage power supply 71, the developing high voltage power supply 72, the exposure unit 73, and the transfer high voltage power supply 74 are connected to the control unit 202, and the control unit 202 controls each of them. Then, this flow path pattern image forming unit 100 forms a flow path pattern image on the porous substrate S1 based on an electrical image signal input from a host device to the controller 200. In addition, examples of the host device include an image reader, a personal computer (hereinafter also referred to as a personal computer), a facsimile, and a smartphone.

<Developing device>
Next, as an example of the developing device, the configuration of the portion related to the developing process of the developing device 20 will be described in detail with reference to FIG.
The developing device 20 includes a developer container 21 having an opening facing the photosensitive drum 11. The developer container 21 contains resin particles instead of toner used in normal electrophotographic devices.

The developing device 20 includes a developing roller 23 and a resin particle supply roller 24. The developing roller 23 carries and transports the COC particles to the electrostatic latent image on the photosensitive drum 11. The developing roller 23 may be a roller having a surface layer with roughening particles dispersed on the surface of an elastic layer. The transportability of the resin particles can be adjusted by the surface roughness of the developing roller 23. In the examples described below, a roller having a surface layer containing 10 μm diameter particles with urethane rubber as a binder on the surface of an elastic layer made of silicone rubber was used. The surface roughness Ra was 3.5 μm.

The supply roller 24 has a foam layer that rubs against the surface of the developing roller 23, and serves to supply the COC particles in the developer container 21 to the developing roller 23. The supply roller 24 is electrically connected to the developing roller 23 to equalize the potential. The developing device 20 also includes a developing blade 25 that is a developer regulating member that regulates the COC particles A supplied to the developing roller 23.
The developing blade 25 may be, for example, a thin stainless steel (SUS) plate supported by a supporting plate. The developing blade 25 is also electrically connected to the developing roller 23, and has the same potential. In the examples described below, a developing blade 25 made of a stainless steel (SUS) plate having a thickness of 80 μm supported by a supporting plate having a thickness of 1 mm was used. The tip of the SUS plate of the developing blade 25 was brought into contact with the developing roller 23 with a pressure of 25 to 35 g/cm. The direction of contact was the counter direction, with the tip of the free end side relative to the contact portion being located upstream in the rotation direction of the developing roller 23. With the above configuration, the surface of the developing roller 23 after passing the developing blade 25 was controlled so that about 0.50 mg/ ^cm2 of developer was coated.

Example 1
In this embodiment, resin particles (hereinafter also referred to as "COC particles A") made from a cyclic olefin copolymer (manufactured by Polyplastics Co., Ltd., TM grade, hereinafter also referred to as "COC-A") obtained by copolymerizing ethylene and a cyclic olefin were used as the developer.
This cyclic olefin copolymer has two types of units (ethylene unit and norbornene unit) represented by the following formula (1-1). In the formula, the molar ratio of x and y is 85:15. Note that formula (1-1) indicates that two types of units are bonded in a predetermined ratio, but does not mean that the copolymer has a block polymer structure in which a polyethylene portion and a polynorbornene portion are bonded.

<Flow path pattern>
In this embodiment, the flow path pattern 80 shown in FIG. 5(a) was formed by placing COC particles A on the porous substrate S1 using the flow path pattern image forming unit 100 to form a COC particle A image. The symbols in FIG. 5(a) are as follows. COC particle A image 81, reagent portion 83 to which a reagent is attached, test liquid portion 84 to which a test liquid is attached, and flow path 82 connecting the reagent portion 83 and the test liquid portion 84. The width L1 of the COC particle A image 81 sandwiching the flow path 82 is 4 mm, and the width L2 of the flow path 82 is 1.5 mm. However, the shape and size of the flow path pattern are not limited to these, and may be a combination of straight lines and curves, or a shape using branches, and the width of the flow path may be changed.

An example of a flow path pattern having curves and branches is shown in FIG. 5(b). In this example, reagent sections 85b, 85c, and 85d for applying reagents and test liquid section 85a for applying test liquid are connected by flow path 85e.

<Heating process>
The porous substrate S1 on which the flow path pattern 80 is formed undergoes a heating process by a heating unit. Through the heating process, the COC particles A melt and permeate into the porous substrate S1, forming a microchannel device having a flow path surrounded by a hydrophobic wall.
The heating temperature must be a temperature at which the COC particles A melt and permeate into the porous substrate S1. In the configuration of this embodiment, the COC particles A permeated into the porous substrate S1 at 140° C. or higher.

The heating time is required to be long enough for the molten COC particles A to completely penetrate the porous substrate S1 in the thickness direction, but if the heating time is too long, the particles may diffuse more than necessary, and the flow paths 82 after the heating process may become narrower than the flow path pattern formed. In the configuration of this embodiment, a heating time of 1 to 10 minutes was used to form an appropriate flow path wall.
In view of the above, the heating conditions in this embodiment were set to 2 minutes in an environment of 200° C. As the heating unit, an oven (Yamato Scientific Co., Ltd. constant temperature incubator DN610H) was used. However, the heating method is not limited to this, and a far-infrared heater or a hot plate may be used, and the heating conditions should be selected according to the physical properties of the COC particles A and the porous substrate S1.

The heating process under the above conditions will be described with reference to FIGS.
As a diagram showing COC particle A before and after heating, a schematic cross-sectional view taken along the broken line 80a in Fig. 5 is shown in Fig. 1. Fig. 1(a) is the cross-sectional view before heating, and Fig. 1(b) is the cross-sectional view after heating.
1(a), the COC particles A at the time of forming the flow path pattern are merely attached to the surface of the porous substrate S1, and no resin particles T are attached to the region 92 that will become the flow path 82. The resin particles T (COC particles A) are melted by subsequent heating, and the melted resin particles T penetrate into the porous substrate S1 by capillary action.
After heating at 200°C for 2 minutes, as shown in Figure 1 (b), the hydrophobic COC particles A penetrate into the porous substrate S1 in the thickness direction, and a flow path 82 sandwiched between the molten and penetrated resin T' is formed in the porous substrate S1.
As described above, by using the flow path pattern image forming unit 100 and the heating unit, a micro flow path device having a flow path surrounded by a hydrophobic wall in the porous substrate S1 can be manufactured.

When using a microfluidic device created based on the flow channel pattern of FIG. 5(a), for example, a chemical that exhibits a color reaction is applied to the reagent section 83, and then the test liquid is applied to the test liquid section 84. The applied test liquid diffuses to the reagent section 83 through the flow channel 82. The test device or the tester can confirm the color reaction that occurs at that time. For example, in the case of a blood glucose test, the test liquid can be blood, and the reagent can be a mixture of oxidase, peroxidase, and potassium iodide, and in the case of a uric acid test, the test liquid can be blood, and the reagent can be a mixture of uricase, peroxidase, and 4-aminoantipyrine.
An example of use of the microchannel device created based on the flow channel pattern of FIG. 5B will be described. After attaching reagent b to reagent portion 85b, reagent c to reagent portion 85c, and reagent d to reagent portion 85d, the test liquid is attached to the test liquid portion 85a. The test liquid attached to the test liquid portion 85a then permeates the flow channel 85e, but by branching on the way, it reacts only with reagent b in reagent portion 85b, only with reagent c in reagent portion 85c, and only with reagent d in reagent portion 85d. By using the branched flow channel, it is possible to simultaneously test the reaction to multiple reagents. In addition, by making the flow channel curved, like the flow channel toward reagent portion 85d, it is possible to eliminate or reduce the accumulation of the test liquid at the edge portion.

<COC Particles A>
Since COC-A used as the resin particle material in this embodiment has very low water absorption, it is unlikely to cause problems such as leakage of specimens or test liquids out of the flow path, or swelling of the flow path when used in a high humidity environment. In addition, since it has high mechanical strength, even if a flow path is formed in a porous substrate such as filter paper that is easily deformed when the device is used, cracks in the flow path wall due to deformation are unlikely to occur.
Furthermore, since no substances harmful to the human body are generated when melting the material to form the flow path wall shape, the material is also highly safe for the human body.

<Solvent resistance>
Next, we will explain the solvent resistance of COC-A. Microchannel devices are used by allowing various specimens and test liquids to permeate the channels through capillary action. If the channel walls become miscible with the specimen or test liquid and swell or undergo a chemical change, the channel structure will collapse, preventing proper capillary action and changing the properties of the specimen or test liquid, making it difficult to obtain correct test results.
For example, in medical testing, blood glucose level tests use acidic hydrogen peroxide as a test agent. In food additive testing, sodium nitrite, which shows alkaline properties as a coloring agent, and ester compounds, which are used as emulsifiers, may be used as samples. As such, paper microanalytical devices are required to use a variety of solvents, including acidic, alkaline, and ester-based solvents, as samples and test solutions, so for analytical devices with a wide range of applications, it is important that they are resistant to these solvents.

Table 1 shows the results of the solvent resistance of COC-A and other resin materials.
Each resin pellet (diameter 3.5 inches, thickness 1 mm) was completely immersed in each solvent for 1 hour under conditions of a temperature of 23° C. and a relative humidity of 50%, and if the pellet dissolved or obvious expansion was observed, it was judged to be NG.

The UV curable ink is an acrylic resin-based UV curable ink, and more specifically, is as follows.
It is made of a mixture of octadecyl acrylate, which is a photoradical polymerizable monomer, and 1,10-bis(acryloyloxy)decane, which is a photoradical polymerizable oligomer.

COC-A is resistant to a wide range of solvents, including not only acids and alkalis but also alcohols, ketones, and esters, making it suitable for use as a highly versatile microfluidic device that can be used with a variety of specimens and test solutions.

<Hydrophobicity>
Pellets (diameter 3.5 inches, thickness 1 mm) of each resin were prepared and immersed in distilled water at 23° C. for 24 hours. The change in mass of each resin when immersed is shown in Table 2 as the water absorption rate.

表２に示すように、ＣＯＣ－Ａは一般的な流路壁材料と比較しても高い疎水性を持つ。

As shown in Table 2, COC-A has a higher hydrophobicity than general flow channel wall materials.

A method for producing COC particles A using COC-A having the above characteristics will be described. COC particles A are particles obtained by crushing resin pellets of COC-A, classifying them so that the volume average particle size is 6 μm, and then thermally spheroidizing them. 1.6 mass% of hydrophobic silica fine particles with a particle size of 10 nm are added to the surface as an external additive. By coating the surface of the COC particles A with the external additive, negative charging performance is improved, and minute gaps can be provided between the COC particles A, improving fluidity and achieving stable flow path pattern image formation. Note that the silica fine particles used as the external additive have been hydrophobized and the amount of external addition is small, so that they do not affect the flow path when finally used as a micro-flow path device. However, the amount of external addition and the substance to be externally added are not limited to these, and may be selected appropriately depending on the configuration of the developing device, such as the developer carrier and developer regulating member used.

<Porous substrate>
The porous substrate S1 is preferably one that exhibits moderate porosity and hydrophilicity. The porous structure is preferably one that has an open cell or mesh (nanofiber, etc.) structure, and examples thereof include filter paper, plain paper, high-quality paper, watercolor paper, Kent paper, synthetic paper, synthetic resin porous film, fabric, and textile products. Among these, filter paper is preferred because it has high porosity and good hydrophilicity.
The porosity can be appropriately selected depending on the purpose, but is preferably 20% to 90%. When the porosity is in the above range, a good balance between the strength as a base material and the permeability of a sample liquid is achieved.

Hydrophilicity is a necessary property for allowing a biological fluid containing water, such as blood, urine, or saliva, as a sample liquid, to diffuse into the substrate.
The average thickness of the porous substrate is generally 0.01 mm to 0.3 mm. If the average thickness is 0.01 mm or more, the substrate has adequate strength. If the average thickness is 0.3 mm or less, the COC can easily penetrate and the flow path wall can be easily formed. However, the average thickness may be selected according to the application, and a thicker thickness of about 0.6 mm may be used.

Since flow path walls (hydrophobic walls) are formed by infiltrating resin into the pores of the porous substrate and filling the pores with resin, it is preferable that the pores of the porous substrate are sufficiently filled with resin in order to create a flow path in which leakage and seepage are suppressed.
In this example, three types of filter paper made of cellulose fibers having a thickness of 20 μm and different basis weights, S1-1, S1-2, and S1-3, were used as the porous substrate S1. Details are shown in Table 3.
The apparent density (g/cm ³ ) was calculated as (basis weight/thickness×1000), and the porosity (%) was calculated as ((true density−apparent density)/true density×100).

<Evaluation of bending resistance>
The porous substrates S1-1 to S1-3 were used with COC particles A to form a microchannel device with the flow channel pattern of FIG. 5(a) so that the amount of COC in the flow channel wall was 2.0 mg/cm ^2. Bending resistance evaluation was performed.
The microchannel device was folded in half at the position of the dashed line 80a in Fig. 5(a), a weight of 500 g (load area 24 mm x 24 mm) was placed on top, and the weight was moved back and forth 10 times on the folded part. The folded part was opened, and the presence or absence of damage to the flow channel was confirmed with the naked eye, and then water was allowed to penetrate into the flow channel to evaluate seepage. Neither damage nor seepage was confirmed for the microchannel device formed with COC particles A.

<Viscoelastic properties of COC>
The COC used to form the flow passage preferably has predetermined viscoelastic properties (storage modulus G', loss modulus G'').
The storage modulus G' represents the elasticity of an object, and the lower the storage modulus G', the greater the deformation for a certain load. In other words, a low storage modulus G' means that the porous substrate S1 is more susceptible to penetration when a permeation force due to capillary action acts on the porous substrate S1.

The loss modulus G'' represents the viscosity of an object, and the higher the loss modulus, the higher the viscosity (the more viscous the object). High viscosity means that when the speed of the fluid differs at each point in the flow, there is a strong tendency to smooth out the speed to make it uniform. In other words, a high loss modulus G'' means that when the COC penetrates the porous substrate S1, it tries to move at the same speed as the surrounding resin, so there is little uneven penetration within the porous substrate S, i.e., it is less likely to bleed. Uneven temperatures in the porous substrate and uneven sizes of the pores in the porous substrate can cause uneven capillary forces, which can cause the flow path pattern to bleed. For this reason, it is preferable for the COC to have high viscosity and be in a state where it is less likely to bleed at the temperature of the fixing process.

In other words, the resin for forming the flow path walls is preferably one that is in a molten state in the temperature range of the fixing process, with a storage modulus G' that allows penetration into the porous substrate S1, and a loss modulus G'' that suppresses bleeding. However, in general resin materials, at the temperature at which the storage modulus G' allows penetration, the loss modulus G'' becomes too low, and conversely, at the temperature at which the loss modulus G'' suppresses bleeding, the storage modulus G' becomes too high. In this respect, COC is superior, and has a temperature range in which both the storage modulus G' and the loss modulus G'' are suitable values. Detailed physical properties will be described later, but COC-A has suitable melting properties, with a low storage modulus G' of 0.4 Pa and a high loss modulus G'' of 10 Pa at 200°C.

Next, the viscoelastic properties required for the molten resin to quickly permeate the porous substrate S1 without seeping in during the heating process will be described with reference to FIG.
The solid line in FIG. 6( a ) represents the storage modulus G′ of COC particle A when the temperature is changed, and the dotted line in FIG. 6( a ) represents the loss modulus G″ of COC particle A when the temperature is changed.
In measuring the elastic modulus, first, COC particles A were set in a pellet molding die with an outer diameter of 20 mm, a load of 15 tons was applied with a pressurizer, and the amount of COC particles A was adjusted so that the pellet thickness after pressing was 1 mm to prepare a pellet. Next, the prepared pellet (diameter 20 mm, thickness 1 mm) was fixed between the lower plate and the upper plate of a rotational viscoelasticity measuring device AR-G2 (manufactured by TA Instruments). A shear stress of 10 Pa was applied from the upper plate at a cycle of 1 Hz, and the storage elastic modulus G' and loss elastic modulus G'' were calculated from the phase difference with the shear stress as a response at that time. The above measurements were performed between 70°C and 200°C while changing the temperature between the plates at a rate of 2°C/min.

First, looking at the storage modulus G' shown by the solid line in Figure 6 (a), as the temperature rises, COC particles A melt above the glass transition point Tg, and the storage modulus G' rapidly decreases, falling below 14 Pa at 130°C and reaching 0.4 Pa at 200°C. When the storage modulus G' decreases, as described above, the COC penetrates into the porous substrate S1 due to the capillary phenomenon caused by the porous substrate S1. In the configuration of this embodiment, the COC penetrates into the porous substrate S1 at 130°C or higher, at which the storage modulus G' becomes 14 Pa or less, so it is preferable to perform the heating process at a temperature of 130°C or higher.

On the other hand, the loss modulus G'' shown by the dotted line in Figure 6(a) also decreases with increasing temperature, but is still highly viscous at approximately 10 Pa at 200°C. If the loss modulus G'' is 10 Pa or higher, bleeding can be sufficiently suppressed, so from the viewpoint of the loss modulus G'', it is preferable that the temperature in the heating process be 200°C or lower.

In other words, in this case, the heating temperature in the heating process is preferably within the range of 130°C to 200°C. The temperature at which the resin begins to permeate the porous substrate and the temperature at which it becomes difficult to permeate vary depending on the material of the porous substrate, the state of the pores, the material and physical properties of the resin, and the combination of the porous substrate and the resin, and should therefore be adjusted appropriately to suit the configuration actually used. The results of tests in which flow paths were formed by changing the heating temperature are shown in Table 4.

As shown in Table 4, when COC particles A were used, good flow paths were formed at heating temperatures of 130°C and 200°C, but at a heating temperature of 120°C, the storage modulus G' was high, so penetration into the porous substrate was insufficient and it was difficult to form flow paths.

<Summary>
As described above, according to the present invention, a microchannel made of COC-A exhibits high hydrophobicity, high mechanical strength, stability in the human body, and high solvent resistance, and can realize a microchannel device with wide applicability that can be used with a wide range of specimens and test agents.
The COC is not limited to that used in this embodiment.
Furthermore, by using materials such as paper or cloth as the base material, it is possible to realize a microchannel device that is low cost, can be used in a non-electrical environment, is easy to carry and dispose of, and requires no maintenance.

In this embodiment, the COC particle image is formed on the porous substrate S1 by electrophotography, but the method of forming the flow path pattern image is not limited to this. Although the productivity is inferior to that of the electrophotography method, for example, the COC particle image may be formed on the porous substrate S1 by thermal transfer. Even in this case, a microchannel device in which a flow path surrounded by COC is formed can be obtained by going through a heating process that satisfies the following conditions.
Conditions: The storage modulus G' is low enough to allow the molten resin to penetrate by capillary action, and the loss modulus G'' is high enough to prevent bleeding.

Example 2
Instead of COC-A used in Example 1, COC-B (COC: 8007F-600 grade, manufactured by Polyplastics Co., Ltd.) was used.
The flow channel walls in the porous substrate preferably further contain a plastic component. The plastic component is preferably at least one component selected from the group consisting of crystalline resins, waxes, and oils. The storage modulus of the plastic component is preferably lower than the storage modulus of the cyclic olefin copolymer.
In Example 2, 50 parts by mass of a plastic component (paraffin wax HNP-51 (Nippon Seiro Co., Ltd.)) was kneaded per 100 parts by mass of COC-B to obtain a kneaded resin. Using this kneaded resin, resin particles (COC particles B) were obtained in the same manner as in Example 1.

With COC-B alone, there is no temperature range up to 300°C where the storage modulus G' is 14 Pa or less, but by mixing paraffin wax as a plastic component, a temperature range where the storage modulus G' is 14 Pa or less comes into existence. Specifically, the resin particles have the viscoelasticity shown in Figure 6 (b). In this case, in the range from 195°C to 300°C, the storage modulus is 14 Pa or less and the loss modulus is 10 Pa or more.

In general, materials with similar solubility parameters (hereinafter referred to as SP values) have high affinity and mix well. It is preferable that the absolute value of the difference between the SP value of the COC and the SP value of the plastic component is 3.5 or less. By using a plastic component whose SP value difference with respect to the COC is 3.5 or less, the viscoelasticity can be suitably controlled. The SP value can be determined by the Fedors method. In the combination of this embodiment, the absolute value of the difference in SP value is 1.56.

COC particles B were used, and the heating temperature in the heating process was set to 230°C, and flow path walls were formed on the porous substrate in the same manner as in Example 1, forming the flow path pattern shown in Figure 5(a). As shown in Table 5, even when COC particles B were used, they penetrated the porous substrate S1 without bleeding, and good flow path walls were formed.

In addition, when COC is used in combination with a plastic component, it exhibits crack-resistant properties. Therefore, the flow path wall formed using COC particles B is less likely to crack even when deformed. When used in combination with a plastic component, COC that softens at relatively high temperatures is used compared to when COC is used alone. Such COC generally has a large deformation rate (breaking elongation) until breakage, so it is thought that the flow path wall formed by using COC in combination with a plastic component is less likely to crack.

<Durability evaluation>
The durability of the microfluidic device was evaluated with a focus on crack resistance.
The created flow path pattern is wound around a metal cylinder having a specified diameter, and then while maintaining the wound state, each end of the flow path pattern is pulled with a force of 4.9 N, and the flow path pattern is observed with the naked eye to see if cracks have occurred. The diameter of the cylinder is gradually reduced, and the evaluation is repeated until cracks are observed in the flow path pattern.

In the 0.08 mm thick microchannel device produced in Example 2, no cracks were observed until it was wrapped around a 4 mm diameter cylinder, and cracks were first observed when it was wrapped around a 3 mm diameter cylinder. In the 0.08 mm thick microchannel device produced in the same manner using the COC particles A used in Example 1, no cracks were observed until it was wrapped around a 13 mm diameter cylinder, and cracks were first observed when it was wrapped around a 12 mm diameter cylinder. The breaking elongation of COC-A is 1.3, and that of COC-B is 4.5.

Example 3
In Example 3, a microchannel device is manufactured with a protective layer that covers the channel formed using COC. The protective layer is a cover for covering the channel portion between the channel walls. This allows the channel to be a closed system, prevents the sample liquid from drying out, and prevents the sample liquid from sticking to hands, which is expected to improve safety.

In this embodiment, the protective layer contains a cyclic olefin copolymer, which is a copolymer of an alkene and a cyclic olefin. The material forming the flow path wall and the material forming the protective layer are the same material. In other words, the cyclic olefin copolymer contained in the flow path wall and the cyclic olefin copolymer contained in the protective layer are the same cyclic olefin copolymer.
When the material forming the flow channel wall and the material forming the protective layer are the same, the adhesion between the flow channel wall and the protective layer is improved, resulting in a flow channel device with high airtightness. When making a micro flow channel device having the flow channel wall and the protective layer out of the same material, the process of forming the protective layer and the flow channel wall are performed separately.
In Example 3, a porous substrate having a cover film (polyethylene terephthalate (PET) film; Toray Industries, Inc., Lumirror S10, thickness 50 μm) adhered to one side was used as the supporting substrate. By adhering the cover film, drying and contamination on the adhered side can be suppressed. From the viewpoint of achieving both strength and flexibility, the average thickness of the cover film is preferably 0.01 mm or more and 0.5 mm or less.

There are no particular restrictions on the material of the cover film and it can be appropriately selected depending on the purpose. Examples include the following: polyesters such as polyethylene terephthalate (PET) and polyethylene naphthalate (PEN), polycarbonate, polyimide resin (PI), polyamide, polyethylene, polypropylene, polyvinyl chloride, polyvinylidene chloride, polystyrene, styrene-acrylonitrile copolymer, cellulose acetate, etc. These may be used alone or in combination of two or more types. Among these, polyethylene terephthalate (PET) and polyethylene naphthalate (PEN) are particularly preferred.

First, in the same manner as in Example 1, resin particles T (COC particles A) were placed on the surface of the porous substrate S1 to which the cover film (PET film) F was not attached, and melted and penetrated to form flow path walls so as to form the flow path pattern of Figure 5(a) (Figures 7(a) to (b)).
Next, COC particles A were placed at a position covering the flow path 82 in FIG. 5(a) through a flow path pattern image formation process (FIG. 7(c)). Next, heating was performed at 120° C. for 2 minutes. At this temperature, COC-A does not melt sufficiently, so the flow path in the porous substrate is maintained. On the other hand, COC particles A placed on the surface of the porous substrate melt on the surface without penetrating into the substrate. As a result, a protective layer 701 is formed to cover the flow path (FIG. 7(d)).

7(a) to (d), a cover film F is adhered as a support base to one surface of the porous substrate, and a protective layer 701 is formed on the other surface. In this manner, a microchannel device can be obtained in which a protective layer is formed on one surface side of the channel formed by being sandwiched between the channel walls, and the other surface is covered with a support base.
Alternatively, a cover film F may not be adhered to either side of the porous substrate, and a protective layer 701 may be formed on both sides using COC through a process similar to the second formation process shown in FIG. 7(c) and the second heating process shown in FIG. 7(d) (FIG. 7(e)).
In the present embodiment, the resin forming the flow path wall and the resin forming the protective layer are the same resin, but they may be different resins. In the case where different resins are used, it is preferable to use a second hydrophobic resin to prevent the influence of water.
Examples of hydrophobic resins include polystyrene and polycarbonate.

Example 4
In Example 3, a protective layer is formed on the surface of the porous substrate, but the protective layer can also be formed so as to provide a ceiling above the flow channel. In Example 4, such a microchannel device is manufactured.
First, in the same manner as in Example 1, COC particles A were placed on the porous substrate S1 and melted and infiltrated to form flow path walls 801 so as to have the flow path pattern shown in FIG. 5(a) (FIGS. 8(a) to (b)).

Next, COC particles A were placed on the flow path portion 802 in Fig. 5(a) through a flow path pattern image forming process (Fig. 8(c)). Next, heating was performed at 120°C for 30 seconds. During this heating time, the COC particles A melt, but do not penetrate sufficiently, so that a protective layer 803 is formed only on the upper part of the flow path portion 802 (Fig. 8(d)). The heating time can be appropriately adjusted according to the material used and the thickness of the protective layer to be formed.
In the fourth embodiment, the heating time was changed according to the thickness of the protective layer 803, but the protective layer can also be formed by reducing the amount of COC particles placed on the flow path portion to reduce the amount of penetration (FIG. 9). For example, as shown in FIG. 9(a), the amount of COC particles placed on the portion forming the flow path is set to about 1/4 to 1/3 of the amount of COC particles placed on the portion forming the flow path wall, and heated sufficiently. By doing so, the flow path wall 801 and the protective layer 803 are formed, as shown in FIG. 9(b). The protective layer 803 has a thickness of about 1/4 of the thickness of the flow path wall 801, and the lower part of the protective layer 803 becomes the flow path portion 802.

Example 5
In this embodiment, a microfluidic device is manufactured in which a cover layer with a reduced printing rate is provided on the surface of the test liquid section. The protective layer in the above embodiment is formed as a solid image with a printing rate of 100%, but when a cover layer is provided on the surface of the test liquid section, the printing rate is appropriately adjusted within the range of 10 to 90%. By providing a cover layer on the surface of the test liquid section, the amount of test liquid flowing into the test liquid section can be controlled. To significantly reduce the amount of test liquid flowing in, the printing rate of the cover layer should be increased, and to slightly reduce the amount, the printing rate of the cover layer should be decreased.
A specific example of a microchannel device in which a cover layer is provided in the test liquid section will be described below.

First, under the same conditions as in Example 1, a microchannel device having the channel pattern of FIG.
Next, in the same manner as in the step of forming the protective layer in Example 3,
A necessary amount of COC particles is placed to form a protective layer 320 with a printing rate of 100% so as to cover the flow path.
A necessary amount of COC particles is placed on the test liquid portion 310c to form a cover layer 311c with a printing rate of 50%.
A necessary amount of COC particles was placed on the test liquid portion 310b to form a cover layer 311b with a printing rate of 80%.
Thereafter, heating was performed at 120° C. for 2 minutes to form a protective layer 320 and cover layers 311b to 311c on the surface of the porous substrate, completing the microchannel device.

This microchannel device can be used in such a way that when a large amount of test liquid is required, the test liquid is applied from test liquid section 310d, and when a smaller amount, for example, about half the amount of test liquid, is required to flow in, the test liquid is applied from test liquid section 310c.
If the pattern of the cover layer 311c printed on the test liquid portion 310c has a printing rate of 50%, the amount of test liquid flowing into the test liquid portion 310c will be half the amount of the test liquid dropped.
Furthermore, if the pattern of the cover layer 311b printed on the test liquid portion 310b has a printing rate of 80%, the amount of test liquid flowing into the test liquid portion 310b will be about 20% of the amount of test liquid dropped.

4. Transfer roller P. Process cartridge 11. Photosensitive drum 12. Charging roller 14. Cleaning blade 15. Memory 20. Developing device 21. Development container 23. Developing roller 24. Resin particle supply roller 25. Developing blade 71. Charging high voltage power source 72. Development high voltage power source 73. Exposure unit 74. Transfer high voltage power source 75. Contact means 80. Flow path pattern 81. COC resin particle A image 82. Flow path 83. Reagent section 84. Test liquid section 100. Flow path pattern image forming unit

Claims (14)

A microchannel device having a channel and a channel wall in a porous substrate,
The flow channel is a porous substrate region sandwiched between the flow channel walls,
The microchannel device is characterized in that the channel wall contains a cyclic olefin copolymer, which is a copolymer of an alkene and a cyclic olefin. The microchannel device according to claim 1, wherein the cyclic olefin is a cyclic olefin having a crosslinked structure. the alkene is ethylene;
The microchannel device according to claim 2 , wherein the cyclic olefin is norbornene. The microchannel device according to any one of claims 1 to 3, wherein the porosity of the porous substrate is 20% to 90%. The microchannel device according to any one of claims 1 to 4, wherein the channel wall in the porous substrate further contains a plastic component. The microchannel device according to claim 5, wherein the plastic component is at least one component selected from the group consisting of crystalline resin, wax, and oil. The microchannel device according to claim 5 or 6, wherein the storage modulus of the plastic component is lower than the storage modulus of the cyclic olefin copolymer. The microchannel device according to any one of claims 5 to 7, wherein the absolute value of the difference between the solubility parameter of the cyclic olefin copolymer and the solubility parameter of the plastic component is 3.5 or less. The microchannel device according to any one of claims 1 to 8, further comprising a protective layer on at least one surface side portion of the channel . 9. The microchannel device according to claim 1, wherein a protective layer is formed on one surface side portion of the channel , and the other surface is covered with a support base. The microchannel device according to claim 9 or 10, wherein the protective layer contains a cyclic olefin copolymer, which is a copolymer of an alkene and a cyclic olefin. The microchannel device according to claim 11, wherein the cyclic olefin copolymer contained in the channel wall and the cyclic olefin copolymer contained in the protective layer are the same cyclic olefin copolymer. The microchannel device according to any one of claims 9 to 11, wherein the protective layer is formed using a hydrophobic resin different from the resin forming the channel wall. The microchannel device according to any one of claims 1 to 13, wherein the content ratio of the alkene to the cyclic olefin is alkene/cyclic olefin = 20/1 to 1/20.

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