JP7683428B2 - Microchannel chip and method for manufacturing same - Google Patents

Description

The present invention relates to a microchannel chip and a method for manufacturing the same.

In recent years, in the field of chemical industry (particularly the pharmaceutical industry related to the production of medicines and reagents), the development of microchannel chips using tiny containers called micromixers or microreactors has progressed. Microchannel chips are provided with multiple microchannels (microcavities connected to the microchannels). By merging multiple types of fluids in the microcavities through the microchannels, the multiple types of fluids are mixed, or a chemical reaction occurs while mixing.

For example, JP 2015-199340 A (Patent Document 1) discloses such a microchannel chip, which includes a resin substrate having a flow channel on one surface and a coating material bonded to the resin substrate so as to cover the flow channel. The resin substrate having the flow channel can be formed by injection molding using a mold, for example, and in this way, the microchannel chip can be manufactured at low cost.

The surface of a mold for injection molding is usually mirror-finished, and the resin substrate formed using this mold also has a similarly smooth surface. However, if the mold surface is too smooth, the mold release properties after molding can be poor, and molding defects such as curling up of the edges of the flow channel grooves can occur.

JP 2015-199340 A

It is desirable to manufacture microchannel chips at low cost using a resin substrate having flow channels while reducing the occurrence of molding defects during the manufacture of the resin substrate.

As a result of extensive research, the inventors have found that the arithmetic mean curvature Spc of the peaks at the joint surface of the resin substrate with the coating material is related to the likelihood of molding defects occurring during the manufacture of the resin substrate. The present invention is based on this finding.

The microchannel chip according to the present invention comprises:
A resin substrate having a flow channel on one surface thereof;
a covering material bonded to the resin substrate so as to cover the flow channel;
The resin substrate has a joint surface with the coating material that has an arithmetic mean height Sa of 0.1 μm or less and an arithmetic mean apex curvature Spc of 150 mm ⁻¹ or more and 500 mm ⁻¹ or less, as measured in accordance with ISO 25178.

According to this configuration, a micro-channel chip can be manufactured at low cost using a resin substrate having a channel groove. In this case, by setting the arithmetic mean curvature Spc of the peaks at the joint surface of the resin substrate with the coating material to be 150 mm ^-1 or more and 500 mm ^-1 or less, it is possible to improve the releasability after molding without changing the arithmetic mean height Sa itself (usually 0.1 μm or less). This makes it possible to manufacture a micro-channel chip at low cost while making it difficult for molding defects to occur during the manufacture of the resin substrate.

In addition, a method for producing a microchannel chip according to the present invention includes the steps of:
a step of injecting a molten resin into a cavity space in a mold having a first mold and a second mold to form a resin substrate having a flow path groove on one surface thereof;
and bonding a coating material to the resin substrate so as to cover the flow channel.
The method further includes, prior to the step of forming the resin substrate, a step of roughening the inner surfaces of the first mold and the second mold around the sites where the convex streak portions corresponding to the flow channel are formed, among the inner surfaces forming the cavity space, so that the arithmetic mean height Sa measured in accordance with ISO 25178 is 0.1 μm or less and the arithmetic mean curvature Spc of the apex is 250 mm ^-1 or more and 800 mm ^-1 or less.

According to this configuration, a resin substrate having a flow channel on one surface is formed using a mold having a first and second molds, and a micro-channel chip can be manufactured at low cost using the resin substrate. In this case, by setting the arithmetic mean curvature Spc of the peaks on the inner surface around the portion where the convex streak portion corresponding to the flow channel in the first or second mold is formed to be 250 mm ^-1 or more and 800 mm ^-1 or less, it is possible to improve the mold releasability after molding without changing the arithmetic mean height Sa itself (usually 0.1 μm or less). This makes it possible to manufacture micro-channel chips at low cost while making it difficult for molding defects to occur during the manufacture of the resin substrate.

Further features and advantages of the present invention will become more apparent from the following description of exemplary, non-limiting embodiments, which are given with reference to the drawings.

Schematic cross-sectional view of a microchannel chip according to an embodiment. Schematic cross-sectional view of a mold for manufacturing microfluidic chips Schematic cross-sectional view showing one aspect of the molding process Schematic cross-sectional view showing one aspect of the molding process Schematic cross-sectional view showing one phase of the assembly process

An embodiment of a microchannel chip and a method for manufacturing the same will be described with reference to the drawings. As shown in FIG. 1, the microchannel chip 1 of this embodiment includes a resin substrate 2 and a coating material 3 bonded to the resin substrate 2.

The resin constituting the resin substrate 2 can be appropriately selected from those having excellent heat resistance and transparency. The resin substrate 2 can be composed of a resin selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl(meth)acrylate, and polyethylene terephthalate, for example.

The resin substrate 2 has a flow channel 21 on one surface (in this embodiment, the bonding surface 2a with the coating material 3). The number of flow channels 21 may be one or more. When multiple flow channels 21 are provided, the flow channels 21 may be provided in series or in parallel. The flow channel 21 may also have branches. The flow channel 21 may have a width of 1 mm or less and a depth of 0.01 mm or more and 0.5 mm or less. In this way, experiments on a microscale can be performed.

The outer shape and size of the resin substrate 2 can be set appropriately taking into consideration ease of handling and analytical suitability (suitability for analytical methods and analytical equipment). For example, if it is a quadrangle (square or rectangle), each side is preferably 10 mm to 200 mm, and more preferably 10 mm to 150 mm. The outer shape of the resin substrate 2 may be other polygonal, circular, elliptical, etc.

The resin substrate 2 can be produced, for example, by injection molding.

The covering material 3 can be composed of, for example, a resin film or a resin plate. The resin constituting the covering material 3 can be appropriately selected from those having excellent heat resistance and transparency. The covering material 3 can be composed of, for example, a resin selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl(meth)acrylate, and polyethylene terephthalate. The resin constituting the covering material 3 may be the same resin as the resin constituting the resin substrate 2, or it may be a different resin.

The thickness of the coating material 3 is not particularly limited, but can be, for example, 0.01 mm to 1 mm. By having a thickness of 0.01 mm or more, wrinkles and the like are unlikely to occur during bonding, and the flow channel 21 can be sufficiently sealed. Furthermore, by having a thickness of 1 mm or less, good conformability to the irregularities of the resin substrate 2 can be obtained.

The resin substrate 2 and the covering material 3 are laminated so that the bonding surface 2a (the surface on which the flow channel 21 is formed) of the resin substrate 2 is in contact with the bonding surface 3a, which is one surface of the covering material 3. The covering material 3 is bonded to the resin substrate 2 so as to cover the flow channel 21. In this way, a microchannel consisting of the flow channel 21 is formed between the resin substrate 2 and the covering material 3. Such a microchannel chip 1 can be suitably used as a biochip such as a nucleic acid chip, a protein chip, an antibody chip, an aptamer chip, and a glycoprotein chip, or as a microanalysis chip for various chemical analyses.

The resin substrate 2 and the covering material 3 can be bonded together by thermocompression bonding the laminate of the resin substrate 2 and the covering material 3 using a heat press. Alternatively, the resin substrate 2 and the covering material 3 can be bonded together using an adhesive, a pressure sensitive adhesive, an adhesive film, or the like.

The micro-channel chip 1 of this embodiment is characterized in that the arithmetic mean curvature Spc of the peaks of the bonding surface 2a of the resin substrate 2 with the coating material 3 is 150 mm ^-1 or more and 500 mm ^-1 or less. Here, the arithmetic mean curvature Spc of the peaks is a type of parameter that indicates surface roughness, and specifically indicates the average of the principal curvatures of the peaks of the surface. The arithmetic mean curvature Spc of the peaks can be measured in accordance with ISO25178.

If the arithmetic mean curvature Spc of the apex of the joint surface 2a of the resin substrate 2 is less than 150 mm ^-1 , when the resin substrate 2 having the flow channel 21 is produced by injection molding, the surface smoothness is too good, and the mold releasability is rather deteriorated. On the other hand, it is often difficult to make the arithmetic mean curvature Spc of the apex of the joint surface 2a of the resin substrate 2 exceed 500 mm ^-1 under general injection molding conditions. Therefore, by setting the arithmetic mean curvature Spc of the apex of the joint surface 2a of the resin substrate 2 with the coating material 3 to 150 mm ^-1 or more and 500 mm ^-1 or less, the mold releasability when produced by injection molding can be improved without requiring excessively special molding conditions.

The arithmetic mean curvature Spc of the peak of the joint surface 2a of the resin substrate 2 with the coating material 3 is preferably 160 mm ^-1 or more, more preferably 170 mm ^-1 or more, and even more preferably 180 mm ^-1 or more. The arithmetic mean curvature Spc of the peak of the joint surface 2a of the resin substrate 2 with the coating material 3 is preferably 480 mm ^-1 or less, more preferably 460 mm ^-1 or less, and even more preferably 440 mm ^-1 or less.

In the microchannel chip 1 of this embodiment, the arithmetic mean height Sa of the bonding surface 2a of the resin substrate 2 with the coating material 3 is 0.1 μm or less. Here, the arithmetic mean height Sa is another type of parameter that represents surface roughness, separate from the arithmetic mean curvature Spc of the peaks, and represents the average of the absolute values of the differences in height of each point relative to the average plane of the surface. The arithmetic mean height Sa can also be measured in accordance with ISO25178.

Usually, when adjusting the arithmetic mean height Sa for the purpose of improving releasability, if the arithmetic mean height Sa is initially 0.1 μm or less with a mirror finish, it is common to increase it to, for example, about 0.2 μm to 0.5 μm. In contrast, in the micro-channel chip 1 of this embodiment, by setting the arithmetic mean curvature Spc of the peaks at the bonding surface 2a of the resin substrate 2 with the coating material 3 to 150 mm ^-1 or more and 500 mm ^-1 or less, it is possible to improve the releasability after molding while keeping the arithmetic mean height Sa itself at 0.1 μm or less.

The microchannel chip 1 of this embodiment can be manufactured using a mold 5 for injection molding and a heat press machine. For example, the resin substrate 2 is made using the mold 5, and the resin substrate 2 and a separately made coating material 3 are thermocompression-bonded using a heat press machine to manufacture the chip.

As shown in FIG. 2, the mold 5 includes a first mold 5A having a recess 51 and a second mold 5B having a ridge portion 52. The recess 51 corresponds to the outer shape of the resin substrate 2. The ridge portion 52 corresponds to the inner shape of the flow channel 21. When the first mold 5A and the second mold 5B are clamped together, a cavity space C is formed as a space surrounded by the inner surface of the recess 51 (first inner surface 5c) and the inner surface of the second mold 5B around the portion where the ridge portion 52 is formed (second inner surface 5d) (see FIG. 3). The second mold 5B also has a gate 53 that communicates with the cavity space C.

The heat press machine includes a first block and a second block that sandwiches and presses the laminate of the resin substrate 2 and the coating material 3 between the first block and the second block. The first block and the second block each have a built-in heater.

The manufacturing method of the microchannel chip 1 of this embodiment includes a mold adjustment process, a molding process, and an assembly process. These are carried out in the following order: mold adjustment process → molding process → assembly process.

The mold adjustment process is a process for adjusting the surface condition of the mold 5, which has been given a normal mirror finish. In this embodiment, in the mold adjustment process, a process is performed to roughen the inner surfaces (second inner surface 5d of second mold 5B) around the portion where the convex streak portion 52 corresponding to the flow channel 21 is formed, among the inner surfaces that form the cavity space C in the first mold 5A and the second mold 5B. The roughening process can be performed, for example, by blasting.

The material of the abrasive grains used in the roughening treatment (blasting treatment) is not particularly limited, but for example, alumina, silicon carbide, zirconia, glass, nylon, stainless steel, etc. can be preferably used. The average particle size of the abrasive grains is not particularly limited, but can be, for example, 20 μm or less. In addition, the discharge pressure of the abrasive grains during the roughening treatment (blasting treatment) is not particularly limited, but can be, for example, 0.01 MPa or more and 0.6 MPa or less.

By carrying out such a surface roughening treatment, the arithmetic mean curvature Spc of the peaks of the inner surface (second inner surface 5d) around the portion where the convex streak portion 52 of the second mold 5B is formed can be adjusted to 250 mm ^-1 or more and 800 mm ^-1 or less. At this time, the arithmetic mean curvature Spc of the peaks can be adjusted to 250 mm ^-1 or more and 800 mm ^-1 or less while keeping the arithmetic mean height Sa of the portion at 0.1 μm or less. The arithmetic mean curvature Spc and the arithmetic mean height Sa of the peaks can be measured in accordance with ISO25178.

The arithmetic mean curvature Spc of the apex of the inner surface (second inner surface 5d) around the portion where the convex rib portion 52 is formed in the second mold 5B is preferably 260 mm ^-1 or more, more preferably 270 mm ^-1 or more, and even more preferably 280 mm ^-1 or more. Moreover, the arithmetic mean curvature Spc of the apex of the inner surface (second inner surface 5d) around the portion where the convex rib portion 52 is formed in the second mold 5B is preferably 780 mm ^-1 or less, more preferably 760 mm ^-1 or less, and even more preferably 740 mm ^-1 or less.

If the arithmetic mean curvature Spc of the peaks of the inner surface (second inner surface 5d) around the portion where the convex streak portion 52 is formed in the second mold 5B is less than 250 mm ^-1 , the surface smoothness is too good when opening the mold in the subsequent molding step, and the mold releasability is rather deteriorated. On the other hand, it is often difficult to make the arithmetic mean curvature Spc of the peaks of the inner surface (second inner surface 5d) around the portion where the convex streak portion 52 is formed in the second mold 5B exceed 800 mm ^-1 under general roughening treatment (blasting) conditions. Therefore, by setting the arithmetic mean curvature Spc of the peaks of the inner surface (second inner surface 5d) around the portion where the convex streak portion 52 is formed in the second mold 5B to 250 mm ^-1 or more and 800 mm ^-1 or less, the mold releasability after molding can be improved without requiring excessively special roughening treatment (blasting) conditions.

The molding process is a process of forming a resin substrate 2 having a flow channel 21 on one side using a mold 5. In the molding process, as shown in FIG. 3, the first mold 5A and the second mold 5B are clamped together, and molten resin is injected from the gate 53 into the cavity space C formed between them. After cooling, the mold is opened, as shown in FIG. 4, to obtain a resin substrate 2 having a flow channel 21 formed on one side, which has an outer shape corresponding to the recess 51 of the first mold 5A and an inner surface corresponding to the protruding streak portion 52 of the second mold 5B. At this time, as described above, since the second mold 5B has been subjected to a predetermined surface roughening treatment (blasting treatment) in the preceding mold adjustment process, the resin substrate 2 has good releasability from the mold 5, and molding defects are unlikely to occur.

The assembly process is a process of assembling the resin substrate 2 produced in the molding process with the covering material 3 produced separately. In the assembly process, first, as shown in FIG. 5, the covering material 3 is laminated on the resin substrate 2 so as to cover the flow channel 21. The laminate is then placed in a heat press machine to bond the resin substrate 2 and the covering material 3 together by thermocompression bonding. In this way, the microchannel chip 1 shown in FIG. 1 can be successfully manufactured.

The microchannel chip 1 of this embodiment will be described in more detail below with reference to examples and comparative examples. However, the scope of the present invention is not limited to the following examples and comparative examples.

[Comparative Example 1]
A mold for injection molding made of chromium-molybdenum stainless steel was prepared. The inner surface forming the cavity space of this mold was measured for the arithmetic mean height Sa, maximum height Sz, aspect ratio of surface quality Str, arithmetic mean curvature of the peak Spc, and developed area ratio of the interface Sdr. These were measured using a laser microscope VK-X1100 manufactured by Keyence Corporation in accordance with ISO25178. Measurements were performed at 15 points on the mold, and the average values were used as the measured values.

The mold was then used to perform injection molding to produce a resin substrate having a flow channel. When the mold was opened and the resin substrate was removed, it was confirmed that the edge of the flow channel in the resin substrate had curled up (poor demolding). The arithmetic mean height Sa, maximum height Sz, aspect ratio Str of the surface quality, arithmetic mean curvature Spc of the peaks, and developed area ratio Sdr of the interface were measured for the surface on the side on which the flow channel was formed in the obtained resin substrate. The measurement conditions for these were the same as those for the mold described above.

[Example 1]
The mold of Comparative Example 1 was subjected to a blasting treatment using a GMT treatment device manufactured by Fuji Manufacturing Co., Ltd. as a surface treatment to roughen the surface. The inner surface forming the cavity space of the mold after this surface treatment was subjected to various measurements in the same manner as in Comparative Example 1. Furthermore, injection molding was performed using the mold to produce a resin substrate. When the mold was opened and the resin substrate was removed, the mold releasability of the resin substrate was good. Various measurements were also performed on the surface of the obtained resin substrate on the side on which the flow path grooves were formed.

[Example 2]
A mold for injection molding made of chromium vanadium molybdenum stainless steel was prepared, and the mold was subjected to a surface treatment under the same conditions as in Example 1. The inner surface forming the cavity space of the mold after this surface treatment was subjected to various measurements in the same manner as in Comparative Example 1. Furthermore, injection molding was performed using the mold to produce a resin substrate. When the mold was opened and the resin substrate was removed, the releasability of the resin substrate was extremely good. Various measurements were also performed on the surface of the obtained resin substrate on the side on which the flow channel grooves were formed.

These results are shown in the table below.

From these findings, it was confirmed that by adjusting the arithmetic mean curvature Spc of the peaks of the mold surface to 250 mm ^-1 or more and 800 mm ^-1 or less, the releasability of the resin substrate obtained by injection molding using the mold can be improved. Also, looking mainly at the resin substrate, it was confirmed that by having the arithmetic mean curvature Spc of the peaks of the obtained resin substrate surface be 150 mm ^-1 or more and 500 mm ^-1 or less, the releasability from the mold after injection molding can be improved. In these cases, it was confirmed that the arithmetic mean height Sa of both the mold surface and the resin substrate surface was maintained at 0.1 μm or less, just like normal.

The microchannel chip and its manufacturing method have been described in detail above, showing specific embodiments, examples, and comparative examples, but the present invention is not limited thereto. The embodiments disclosed in this specification are illustrative in all respects, and can be modified as appropriate within the scope of the present disclosure.

Reference Signs List 1 Micro-channel chip 2 Resin substrate 2a Bonding surface 3 Coating material 3a Bonding surface 5 Mold 5A First mold 5B Second mold 5c First inner surface 5d Second inner surface 21 Channel groove 51 Recess 52 Convex stripe portion 53 Gate C Cavity space

Claims (2)

A resin substrate having a flow channel on one surface thereof;
a covering material bonded to the resin substrate so as to cover the flow channel;
The micro-channel chip has a joint surface of the resin substrate with the coating material having an arithmetic mean height Sa of 0.1 μm or less and an arithmetic mean apex curvature Spc of 150 mm ⁻¹ or more and 500 mm ⁻¹ or less, as measured in accordance with ISO 25178. a step of injecting a molten resin into a cavity space in a mold having a first mold and a second mold to form a resin substrate having a flow path groove on one surface thereof;
and bonding a coating material to the resin substrate so as to cover the flow channel.
the method for manufacturing a microchannel chip further comprising, prior to the step of forming the resin substrate, a step of roughening the inner surfaces of the first mold and the second mold around a portion where a convex streak portion corresponding to the flow channel is formed, so that an arithmetic mean height Sa measured in accordance with ISO 25178 is 0.1 μm or less and an arithmetic mean curvature Spc of a peak is 250 mm ^-1 or more and 800 mm ^-1 or less.

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