Fluid device, production method for same, and electrophoresis device using same

Abstract

The present invention provides a fluid device that has a lower flow path resistance and more reliably prevents the adhesion of bubbles to an inner wall surface of a flow path than past fluid devices.　This fluid device is a resin fluid device that is to be installed in an analysis device. The fluid device is characterized by containing a tubular flow path that has a circular cross-sectional shape and has an aspect ratio that is a ratio of length and diameter of at least 10, the arithmetic average of the roughness of an inner wall surface of the flow path being no more than 0.5 μm with a standard deviation of no more than 0.1 μm.

Description

Fluidic device, manufacturing method thereof, and electrophoresis apparatus using the same

[0001] The present invention relates to a fluidic device, a method for manufacturing the same, and an electrophoresis apparatus using the same.

[0002] Conventionally, a known fluidic device installed in an analytical instrument involves pressing a mold shaped like a fine channel onto a heat-softened resin substrate, transferring the shape, and then attaching a plate-shaped lid to the substrate (see, for example, Patent Document 1). This fluidic device is difficult to form with a substantially circular cross-sectional shape and low channel resistance, requiring a bonding strength greater than the internal pressure applied to the channel. Fluidic devices with substantially circular channels formed by machining a resin substrate or by a three-dimensional printer are also possible. However, these fluidic devices suffer from minute irregularities on the inner wall surface of the channel due to cutting marks or scanning marks. Such irregularities in the channel can hinder fluid flow and cause air bubbles to adhere to the inner wall surface. Meanwhile, techniques for smoothing the surface irregularities of a resin substrate by applying an organic solvent or resin varnish to the surface have been disclosed (see, for example, Patent Documents 2 and 3). Therefore, it is conceivable to apply substrate surface planarization techniques (see, for example, Patent Documents 2 and 3) to fluidic devices fabricated by machining or a three-dimensional printer.

[0003] Special table 2017-538416 publication JP 6-128398 publication JP 5-198952 publication

[0004] However, even when the smoothing techniques disclosed in Patent Documents 2 and 3 are applied to fluidic devices fabricated by machining or a three-dimensional printer, there is a problem in that organic solvents and the like are difficult to penetrate into the fine flow channels. Another approach is to pressurize the vapor of the organic solvent and forcibly introduce it into the flow channel. However, the organic solvent introduced into the flow channel by pressurization is partially liquefied within the flow channel. The liquefied organic solvent adheres to the inner wall surface of the flow channel at multiple locations along the length of the flow channel. A non-uniformly roughened surface is formed in the flow channel of the fluidic device along the length. This makes it even easier for air bubbles to adhere to the inner wall surface of the flow channel of the fluidic device.

[0005] The object of the present invention is to provide a fluidic device that has lower flow path resistance than conventional devices and more reliably prevents air bubbles from adhering to the inner wall surfaces of the flow paths, a method for manufacturing the same, and an electrophoresis apparatus using the same.

[0006] The fluid device of the present invention is a resin fluid device to be mounted on an analytical instrument, and is characterized in that it has an internal flow path with an aspect ratio (length to diameter) of 10 or more and a circular tubular cross-sectional shape, and the arithmetic mean roughness of the inner wall surface of the flow path is 0.5 μm or less and the standard deviation is 0.1 μm or less.

[0007] In addition, the method for manufacturing a fluidic device of the present invention is a method for manufacturing a fluidic device having an internal flow path that has an aspect ratio, which is the ratio of length to diameter, of 10 or more and a tubular cross-sectional shape with a circular cross-section, and the arithmetic mean roughness of the inner wall surface of the flow path is 0.5 μm or less and a standard deviation of 0.1 μm or less, and is characterized by comprising the steps of: forming a through hole with a circular cross-sectional shape in a resin block; and sucking air from one end of the through hole while introducing vapor of an organic solvent from the other end.

[0008] An electrophoresis apparatus of the present invention includes the above-described fluidic device, and is characterized in that the flow path in the fluidic device constitutes a part of a flow path for electrophoresis.

[0009] According to the present invention, there are provided a fluidic device which has a smaller flow path resistance than conventional devices and prevents air bubbles from adhering to the inner wall surface of the flow path, a method for manufacturing the same, and an electrophoresis apparatus using the same.

[0010] 1 is a structural explanatory diagram of a fluidic device according to a first embodiment of the present invention. Reference numerals 201 to 204 are diagrams illustrating steps in a method for manufacturing the fluidic device shown in FIG. 1. Reference numeral 301 is a cross-sectional view taken along line IIIa-IIIa of the view indicated by reference numeral 204 in FIG. 2. Reference numeral 302 is a cross-sectional view showing a modified example of the flow channel indicated by reference numeral 301. Reference numerals 501 to 504 are diagrams illustrating steps in a method for manufacturing the fluidic device shown in FIG. 4. Reference numerals 701 to 704 are diagrams illustrating steps in a method for manufacturing the fluidic device shown in FIG. 6. Reference numerals 701 to 704 are diagrams illustrating the steps in a method for manufacturing the fluidic device shown in FIG. 6. A structural explanatory diagram of an electrophoresis apparatus using the fluidic device of FIG. 6. FIG. 1 is a graph showing the results of verifying the effects of the fluidic device according to an embodiment of the present invention.

[0011] Hereinafter, a mode (embodiment) for carrying out the present invention will be described in detail with reference to the drawings as appropriate. The fluidic device of this embodiment is mounted on an analytical apparatus for use. The analytical apparatus can be, for example, an electrophoresis apparatus, which will be described in detail later, or any other analytical apparatus. The fluidic device of this embodiment can function as a reagent delivery unit, an optical cell, a microreactor, or the like in such an analytical apparatus.

[0012] <First embodiment> (Fluidic device) Fig. 1 is an explanatory diagram of the configuration of a fluidic device 1A according to a first embodiment of the present invention. As shown in Fig. 1, the fluidic device 1A is also called a polymer block and is a rectangular parallelepiped made of resin. As will be described later, the fluidic device 1A in this embodiment has a resin substrate 11 (see Fig. 3) as a base on which a flow path 23A is formed. The resin substrate 11 corresponds to a "resin block."

[0013] The flow path 23A has a circular cross-sectional shape and is tubular. In this embodiment, the inner diameter of the flow path 23A is assumed to be 0.5 mm or more and 5 mm or less. However, the inner diameter of the flow path 23A is not limited to this and can be changed appropriately depending on the properties of the fluid flowing through the flow path 23A. The aspect ratio of the inner diameter to the length of the flow path 23A (length / inner diameter) is 10 or more.

[0014] The roughness of the inner wall surface of the flow channel 23A over the entire longitudinal direction is 0.5 μm or less in terms of arithmetic mean roughness (Ra) in accordance with ISO 4287-1997. The standard deviation of the roughness of the inner wall surface over the entire longitudinal direction of the flow channel 23A is 0.1 μm or less in terms of root mean square height (Sq) in accordance with ISO 25178. The technical significance of the inner wall surface of the flow channel 23A of the fluidic device 1A of this embodiment having such surface roughness will be explained in detail below, along with the effects of the fluidic device 1A.

[0015] The resin constituting the fluidic device 1A of this embodiment is assumed to be an acrylic resin. However, the resin constituting the fluidic device 1A is not limited to this, and any hard transparent resin can be used. Examples of hard transparent resins include, but are not limited to, polycarbonate, polyarylate, polysulfone, polyimide, polyetherimide, and norbornene resin.

[0016] (Manufacturing Method) Next, a manufacturing method of the fluidic device 1A (see FIG. 1) will be described. Reference numerals 201 to 204 in FIG. 2 are explanatory diagrams of steps in the manufacturing method of the fluidic device 1A shown in FIG. 1. The manufacturing method of this embodiment includes the steps of preparing a resin substrate 11 (resin block) as shown by reference numeral 201 in FIG. 2, forming a through hole 20A having a circular cross section in the resin substrate 11 (resin block) as shown by reference numeral 202 in FIG. 2, and introducing vapor of an organic solvent from the other end 21 b of the through hole 20A while suctioning from one end 21 a of the through hole 20A as shown by reference numeral 203 in FIG. 2.

[0017] As a result, in the drawing of reference numeral 203 in FIG. ＩＮ As shown by the arrows in the figure, the vapor of the organic solvent flows at a predetermined flow rate through the through-hole 20A, which is in a reduced pressure state lower than the atmospheric pressure, and is ＯＵＴAs shown by the arrows, the organic solvent vapor is discharged from the resin substrate 11. During this process, the organic solvent vapor dissolves or softens the minute resin convex portions (not shown) that constitute the rough surface of the through-hole 20A without liquefying, and smooths the convex portions along the direction of the vapor flow. As a result, the rough surface of the through-hole 20A, which is formed by the minute concaves and convexes, is smoothed, thereby completing the fluidic device 1A having the flow path 23A shown in the diagram of reference numeral 204 in FIG. 2.

[0018] In this embodiment, the resin substrate 11 (resin block) is assumed to have a rectangular cuboid shape when viewed from above, but is not limited to this as long as a flow path 23A can be formed inside, and other three-dimensional shapes such as a polygonal prism, a cylinder, a disk, a sphere, etc. can also be used.

[0019] In this embodiment, the method for forming the through hole 20A in the resin substrate 11 (resin block) is assumed to be machining. Specifically, a method is assumed in which a tool such as a drill is used to form a hole (through hole 20A) with a predetermined inner diameter so as to linearly penetrate the resin substrate 11 (resin block). The cross-sectional shape of this through hole 20A is formed in a shape close to the cross-sectional shape of the flow path 23A shown in FIG. 1 , and its aspect ratio is 10 or more. However, the method for forming the through hole 20A in the resin substrate 11 (resin block) is not limited to machining. As will be described later, the resin substrate 11 (resin block) having the through hole 20A can also be formed using a 3D printer.

[0020] An example of a method for introducing organic solvent vapor into through-hole 20A (see the diagram of reference numeral 203 in FIG. 2 ) is to retain the organic solvent vapor in the gas phase of a bath containing the organic solvent at the bottom, and then introduce the organic solvent vapor into through-hole 20A. In this case, it is desirable to generate saturated organic solvent vapor in the gas phase of the bath at a temperature lower than the temperature inside through-hole 20A, i.e., the temperature of resin substrate 11 (resin block).

[0021] Then, as shown in the diagram indicated by reference numeral 203 in FIG. 2 , saturated vapor of the organic solvent is introduced from the other end 21b of the through-hole 20A while suction is applied from one end 21a using a vacuum pump or the like. This, combined with the fact that the internal pressure of the through-hole 20A becomes lower than atmospheric pressure, more reliably prevents the organic solvent vapor from liquefying within the through-hole 20A. Note that in this embodiment, the temperature of the resin substrate 11 (resin block) in the step indicated by reference numeral 203 in FIG. 2 is assumed to be room temperature (25°C), but it can also be set higher than room temperature (25°C). In this case, the temperature of the vapor phase in the organic solvent bath can be set to a temperature lower than the temperature of the resin substrate 11 (resin block) or higher than room temperature (25°C).

[0022] In this embodiment, the organic solvent is assumed to be dichloromethane, which can dissolve or soften the acrylic resin that constitutes the resin substrate 11 (resin block), but is not limited to this. Therefore, depending on the type of resin that constitutes the resin block, an organic solvent that generates vapor capable of dissolving or softening the resin, preferably at room temperature (25°C) under atmospheric pressure, can be selected as the organic solvent. Examples of such organic solvents include, but are not limited to, halogenated hydrocarbons with a low carbon number, ketones with a low carbon number (e.g., acetone), and cyclic ethers (e.g., tetrahydrofuran).

[0023] The view indicated by reference numeral 301 in Fig. 3 is a cross-sectional view taken along line IIIa-IIIa of the view indicated by reference numeral 204 in Fig. 2. The view indicated by reference numeral 302 in Fig. 3 is a cross-sectional view showing a modified example of the flow path indicated by reference numeral 301 in Fig. 3. According to this manufacturing method, the inner wall surface of the through-hole 20A (see the view indicated by reference numeral 203 in Fig. 2) is smoothed over the entire longitudinal direction, and a flow path 23A having a circular cross-sectional shape and an aspect ratio of 10 or more is formed inside the resin substrate 11 (resin block) indicated by reference numeral 204 in Fig. 2.

[0024] The flow path 23A shown in the diagram of reference numeral 301 in Fig. 3 has an inner wall surface 23A1 whose roughness has an arithmetic mean of 0.5 µm or less and a standard deviation of 0.1 µm or less. Also, as shown in the diagram of reference numeral 302 in Fig. 3, the inner wall surface 23A1 of the flow path 23A has a SiO ２It is assumed that a coating layer L made of a SiO film is formed on the inner wall surface 23A1. ２ The film is formed by depositing SiO ２ It is formed by applying a particle dispersion or a silicon alkoxide solution.

[0025] SiO ２ SiO using particle dispersion ２ The film is formed by applying SiO ２ It is formed by evaporating the dispersion medium from the particle dispersion liquid. SiO ２ The film is formed by a hydrolysis reaction of silicon alkoxide on the inner wall surface 23A1. Examples of silicon alkoxide include, but are not limited to, tetramethoxysilane, tetraethoxysilane, tetraisopropoxysilane, and tetrapropoxysilane.

[0026] (Effects) Next, the effects of the fluidic device 1A of this embodiment and its manufacturing method will be described. The fluidic device 1A of this embodiment has an aspect ratio (length-to-diameter ratio) of 10 or more and an internal flow path 23A that is tubular and has a circular cross-sectional shape. The arithmetic mean roughness of the inner wall surface 23A1 of the flow path 23A is 0.5 μm or less and a standard deviation of 0.1 μm or less. Because the aspect ratio of this fluidic device 1A is 10 or more, the fluidic device 1A can extend the residence time of reagents and specimens (samples) in the flow path 23A. This allows the fluidic device 1A to thoroughly mix and react the reagents and specimens (samples) within the flow path 23A. This effect is advantageous when the fluidic device 1A functions as a liquid delivery unit of an analytical device or a microreactor.

[0027] Furthermore, in the fluidic device 1A, the cross-sectional shape of the flow path 23A is circular, and therefore, unlike conventional fluidic devices (see, for example, Patent Document 1), the flow path 23A has no corners. This allows the fluidic device 1A to reduce flow path resistance when a fluid flows through the flow path 23A. Furthermore, because the flow path 23A of the fluidic device 1A has no corners, the flow of the fluid is not affected and adhesion of air bubbles to the inner wall surface is suppressed.

[0028] Furthermore, the fluidic device 1A has an inner wall surface roughness of the flow channel 23A with an arithmetic mean of 0.5 μm or less and a standard deviation of 0.1 μm or less, thereby suppressing not only adhesion of air bubbles to the inner wall surface of the flow channel 23A but also adhesion of compounds contained in reagents and biological substances contained in specimens. Therefore, this fluidic device 1A can prevent a decrease in the reliability of analysis results due to the gradual accumulation of compounds and biological substances on the inner wall surface of the flow channel 23A. Furthermore, the fluidic device 1A can more reliably prevent the gradual accumulation of compounds and biological substances from clogging the flow channel 23A.

[0029] Unlike the fluidic device 1A of this embodiment, if the surface roughness of the inner wall surface of the flow channel is high even locally, compounds and biological materials are likely to adhere to those areas. The compounds and biological materials gradually accumulate, reducing the reliability of the analysis results and causing blockage of the flow channel. These effects are advantageous when the fluidic device 1A functions as a liquid delivery unit or a microreactor in an analytical apparatus.

[0030] Furthermore, in the fluidic device 1A, the arithmetic mean roughness of the inner wall surface of the flow channel 23A is 0.5 μm or less, thereby reducing light scattering on the surface of the flow channel 23A. This improves the reaction efficiency of the photochemical reaction of the reagent or specimen within the flow channel 23A. Furthermore, in the fluidic device 1A, the arithmetic mean roughness of the inner wall surface of the flow channel 23A is 0.5 μm or less, thereby improving the light detection sensitivity of the luminescence reaction within the flow channel 23A. These effects are advantageous when the fluidic device 1A functions as an optical cell of an analytical instrument.

[0031] In addition, in such a fluidic device 1A, the resin is preferably an acrylic resin. This fluidic device 1A provides excellent moldability of the resin substrate 11 (resin block) that serves as the base, and facilitates machining to form the through-holes 20A in the resin substrate 11. This fluidic device 1A also provides a wide range of organic solvents to be introduced into the through-holes 20A.

[0032] In addition, in such a fluidic device 1A, the inner wall surface 23A1 of the flow channel 23A is made of SiO ２ According to this fluidic device 1A, the surface energy of the flow path 23A is increased, and adhesion of air bubbles can be more reliably suppressed.

[0033] Furthermore, a manufacturing method for such a fluid device 1A is a fluid device 1A having an internal flow path 23A that has an aspect ratio, which is the ratio of length to diameter, of 10 or more and a tubular cross-sectional shape with a circular cross-section, and the arithmetic mean roughness of the inner wall surface of the flow path 23A is 0.5 μm or less and a standard deviation of 0.1 μm or less, and includes the steps of forming a through hole 20A with a circular cross-sectional shape in a base made of a resin substrate 11 (resin block), and introducing vapor of an organic solvent from the other end 21b of the through hole 20A while applying suction from one end 21a.

[0034] According to this manufacturing method, organic solvent vapor is introduced into the through hole 20A by suction from one end 21a of the through hole 20A, so that organic solvent vapor can be easily introduced even into through holes 20A with a high aspect ratio, such as an aspect ratio of 10 or more.

[0035] Furthermore, according to this manufacturing method, the organic solvent vapor is introduced into the through-hole 20A by suction from the one end 21a side of the through-hole 20A, so that the organic solvent vapor is introduced into the through-hole 20A at a reduced pressure lower than atmospheric pressure. This prevents the organic solvent vapor from liquefying within the through-hole 20A. The flow path 23A is smoothed without deformation throughout its entire longitudinal length. Furthermore, according to this manufacturing method, it is possible to reliably and efficiently manufacture a fluidic device 1A having an aspect ratio (the ratio of length to diameter) of 10 or more, a flow path 23A with a circular tubular cross-sectional shape, and an inner wall surface roughness of the flow path 23A with an arithmetic mean of 0.5 μm or less and a standard deviation of 0.1 μm or less.

[0036] In addition, in the manufacturing method of the fluidic device 1A, the through-hole 20A is preferably formed by machining the resin substrate 11 (resin block). This manufacturing method makes it possible to easily and accurately form the through-hole 20A having a predetermined aspect ratio in the resin substrate 11 (resin block).

[0037] In addition, in the manufacturing method of the fluidic device 1A, it is preferable that the resin constituting the resin substrate 11 (resin block) is an acrylic resin and the organic solvent is dichloromethane. This manufacturing method makes it possible to efficiently form the flow channel 23A in the resin substrate 11 (resin block) with an arithmetic mean roughness of the inner wall surface of 0.5 μm or less and a standard deviation of 0.1 μm or less.

[0038] In addition, in the manufacturing method of such a fluidic device 1A, after the step of introducing the vapor of the organic solvent into the through-hole 20A, SiO ２ According to this manufacturing method, it is preferable to further include a step of forming a SiO ２ The film allows the flow path 23A to be formed with a large surface energy, which more reliably prevents air bubbles from adhering to the flow path 23A of the fluidic device 1A.

[0039] Second Embodiment (Fluidic Device) Next, a fluidic device according to a second embodiment of the present invention will be described. In this embodiment, the same components as those in the fluidic device 1A according to the first embodiment (see FIG. 1) are designated by the same reference numerals, and detailed descriptions thereof will be omitted.

[0040] 4 is a diagram illustrating the configuration of a fluidic device 1B according to a second embodiment of the present invention. As shown in FIG. 4, in the fluidic device 1B, a flow path 23B formed inside a resin substrate 11 (resin block) made of acrylic resin is formed so as to be curved. However, the resin substrate 11 is not limited to acrylic resin, and the aforementioned hard transparent resin can also be used.

[0041] The flow path 23B is composed of a first flow path portion 23B1 that extends linearly and a second flow path portion 23B2 that also extends linearly. The first flow path portion 23B1 and the second flow path portion 23B2 are connected inside the resin substrate 11 (resin block) so as to form an included angle with each other. As a result, the first flow path portion 23B1 and the second flow path portion 23B2 are integrated to form a single hole that penetrates the resin substrate 11 (resin block). Note that the angle formed between the first flow path portion 23B1 and the second flow path portion 23B2 can be set in a range greater than 0 degrees and less than 180 degrees, but in this embodiment, the angle formed between the first flow path portion 23B1 and the second flow path portion 23B2 is set to 120 degrees.

[0042] The cross-sectional shape of such flow path 23B is circular. Furthermore, in this embodiment, the inner diameter of flow path 23B is assumed to be 0.5 mm or more and 5 mm or less. However, the inner diameter of flow path 23B is not limited to this and can be changed appropriately depending on the properties of the fluid flowing through flow path 23B. Furthermore, the aspect ratio of the inner diameter to the length of flow path 23B (length / inner diameter) is 10 or more.

[0043] The roughness of the inner wall surface of the flow path 23B over the entire lengthwise area is 0.5 μm or less in terms of arithmetic mean roughness (Ra) in accordance with ISO 4287-1997. The standard deviation of the roughness of the inner wall surface over the entire lengthwise area of ​​the flow path 23B is 0.1 μm or less in terms of root mean square height (Sq) in accordance with ISO 25178. The inner wall surface of the flow path 23B is coated with a SiO ２ It is assumed that a coating layer L (see the diagram of reference numeral 302 in FIG. 3) made of a film is provided.

[0044] (Manufacturing Method) Next, a manufacturing method of the fluidic device 1B (see FIG. 4) will be described. Reference numerals 501 to 504 in FIG. 5 are explanatory diagrams of steps in the manufacturing method of the fluidic device 1B shown in FIG. 4. The manufacturing method of this embodiment includes the steps of preparing a resin substrate 11 (resin block) as shown by reference numeral 501 in FIG. 5, forming a through hole 20B having a circular cross section in the resin substrate 11 (resin block) as shown by reference numeral 502 in FIG. 5, and introducing vapor of an organic solvent from the other end 21 d of the through hole 20B while suctioning from one end 21 c of the through hole 20B as shown by reference numeral 503 in FIG.

[0045] In the step of forming the through hole 20B shown in the drawing of reference numeral 502 in Fig. 5, the through hole 20B is drilled from both the one end 21c side and the other end 21d side with a tool such as a drill to form a bent through hole 20B. In the step of introducing the vapor of the organic solvent into the through hole 20B, the V ＩＮ As shown by the arrows in the figure, the vapor of the organic solvent flows at a predetermined flow rate through the through-hole 20B, which is in a reduced pressure state lower than the atmospheric pressure, and is ＯＵＴ As shown by the arrows in the figure, the organic solvent vapor is discharged from the resin substrate 11. During this process, the organic solvent vapor dissolves or softens the minute resin convex portions (not shown) that constitute the rough surface of the through-hole 20B without liquefying, and smooths the convex portions along the direction of the vapor flow. As a result, the rough surface of the through-hole 20B, which is formed by the minute concaves and convexes, is smoothed, thereby completing the fluidic device 1B having the flow path 23B shown in the diagram of reference numeral 504 in FIG. 5.

[0046] (Effects) Next, the effects of the fluidic device 1B of this embodiment and the manufacturing method thereof will be described. The fluidic device 1B of this embodiment has an aspect ratio (length to diameter) of 10 or more, an internal flow path 23B that is a tubular shape with a circular cross section, and the arithmetic mean roughness of the inner wall surface of the flow path 23B is 0.5 μm or less and a standard deviation of 0.1 μm or less, thereby achieving the same effects as the fluidic device 1A of the first embodiment.

[0047] Furthermore, the fluidic device 1B of this embodiment has a bent flow path 23B. According to this fluidic device 1B and its manufacturing method, the positions of the fluid outlet and inlet in the flow path 23B of the fluidic device 1B can be changed by changing the angle between the first flow path portion 23B1 and the second flow path portion 23B2. According to this fluidic device 1B and its manufacturing method, it is possible to obtain a fluidic device that has improved flexibility in placement within an analytical apparatus.

[0048] Third Embodiment (Fluidic Device) Next, a fluidic device according to a third embodiment of the present invention will be described. In this embodiment, the same components as those in the fluidic device 1A according to the first embodiment (see FIG. 1) are designated by the same reference numerals, and detailed descriptions thereof will be omitted.

[0049] FIG. 6 is an explanatory diagram of the configuration of a fluidic device 1C according to a third embodiment of the present invention. As shown in FIG. 6, the fluidic device 1C has a flow path 23C formed inside a resin substrate 11 (resin block) made of acrylic resin. However, the resin substrate 11 is not limited to acrylic resin, and the aforementioned hard transparent resin can also be used. In this embodiment, the resin substrate 11 (resin block) is formed in a rectangular parallelepiped shape. The flow path 23C is composed of multiple flow paths, including flow path 23C1, flow path 23C2, flow path 23C3, and flow path 23C4.

[0050] The fluidic device 1C also has recesses 24 and 25 that open onto the surface of the resin substrate 11 (resin block). These two recesses 24 and 25 are formed as cylindrical spaces with bottoms. The surface on which the recess 24 opens and the surface on which the recess 25 opens are positioned perpendicular to each other.

[0051] The flow path 23C1 extends linearly from one side surface of the resin substrate 11 toward the interior of the resin substrate 11. The flow path 23C2 has its base end at an end of the flow path 23C1 formed inside the resin substrate 11, and extends to form an L with the flow path 23C1. The tip end of the flow path 23C2 is connected to the bottom surface of the recess 25. The flow path 23C3 extends linearly from one end connected to the bottom surface of the recess 24 toward the interior of the resin substrate 11. The other end of the flow path 23C3 is connected to the inner circumferential surface of the recess 24.

[0052] The flow path 23C4 extends linearly from one side surface of the resin substrate 11 toward the inside of the resin substrate 11 so as to be parallel to the flow path 23C1, and is connected to the inner circumferential surface of the recess 24. That is, in the fluid device 1C, of ​​the multiple flow paths that make up the flow path 23C, which are made up of the flow path 23C1, the flow path 23C2, the flow path 23C3, and the flow path 23C4, the flow path 23C2 and the flow path 23C3 communicate with each other via the recess 25, and the flow path 23C3 and the flow path 23C4 communicate with each other via the recess 24.

[0053] The cross-sectional shape of such flow path 23C is circular. Furthermore, in this embodiment, the inner diameter of flow path 23B is assumed to be 0.5 mm or more and 5 mm or less. However, the inner diameter of flow path 23C is not limited to this and can be changed appropriately depending on the properties of the fluid flowing through flow path 23C. Furthermore, the aspect ratio of the inner diameter to the length of flow path 23C (length / inner diameter) is 10 or more.

[0054] The roughness of the inner wall surface of the flow path 23C over the entire longitudinal direction is 0.5 μm or less in terms of arithmetic mean roughness (Ra) in accordance with ISO 4287-1997. The standard deviation of the roughness of the inner wall surface over the entire longitudinal direction of the flow path 23C is 0.1 μm or less in terms of root mean square height (Sq) in accordance with ISO 25178. The arithmetic mean roughness (Ra) of the inner wall surfaces of the recesses 24 and 25 is also 0.5 μm or less, and the root mean square height (Sq) is 0.1 μm or less. The inner wall surfaces of the flow path 23C and the inner wall surfaces of the recesses 24 and 25 are coated with SiO ２It is assumed that a coating layer L (see the diagram of reference numeral 302 in FIG. 3) made of a film is provided.

[0055] (Manufacturing Method) Next, a manufacturing method of the fluidic device 1C (see FIG. 6) will be described. Reference numerals 701 to 704 in FIG. 7 are explanatory diagrams of steps in the manufacturing method of the fluidic device 1C shown in FIG. 6. The manufacturing method of this embodiment includes the steps of preparing a resin substrate 11 (resin block) as shown by reference numeral 701 in FIG. 7, forming a through hole 20C having a circular cross section in the resin substrate 11 (resin block) as shown by reference numeral 702 in FIG. 7, and introducing vapor of an organic solvent into the through hole 20C while suctioning from one end 21e, 21f, 21g of the through hole 20C as shown by reference numeral 703 in FIG.

[0056] In this manufacturing method, recesses 24 and 25 are formed in the resin substrate 11 using a drill or the like. Then, through holes 20C having a circular cross-sectional shape are formed by machining. In the step of forming through holes 20C shown in FIG. 7 at 702, through hole 20C1 is formed by drilling from one end 21h of through hole 20C1 using a tool such as a drill. Through hole 20C2 is formed by drilling from one end 21e of through hole 20C2 using a tool such as a drill. Through hole 20C3 is formed by drilling from one end 21f of through hole 20C3 using a tool such as a drill. Through hole 20C4 is formed by drilling from one end 21g of through hole 20C4 using a tool such as a drill.

[0057] In addition, in the process of introducing the organic solvent vapor into the through-hole 20C, as shown in the diagram of reference numeral 703 in Fig. 7, the through-holes 20C1, 20C2, and the through-hole 20C3 are sucked through the recess 25 that communicates with one end 21e of the through-hole 20C1 and one end 21f of the through-hole 20C3. The through-hole 20C4 is sucked through one end 21g. As a result, in the diagram of reference numeral 703 in Fig. 7, the mark V ＩＮ As shown by the symbol V, the vapor of the organic solvent is introduced from the recess 24 and one end 21h of the through-hole 20C1 under a reduced pressure lower than atmospheric pressure. ＯＵＴ As indicated by , the liquid is discharged from the recess 25 and one end 21g of the through-hole 20C4.

[0058] At this time, the organic solvent vapor dissolves or softens the minute resin convex portions (not shown) that make up the rough surface of the through-hole 20C (see the diagram of reference numeral 702 in FIG. 7 ) without liquefying, and smooths the convex portions along the direction of the vapor flow. As a result, the rough surface of the through-hole 20C (see the diagram of reference numeral 702 in FIG. 7 ) formed with minute concavities and convexities is smoothed, thereby completing the fluidic device 1C (see FIG. 6 ) having the flow path 23C shown in the diagram of reference numeral 704 in FIG. 7 .

[0059] (Electrophoresis Apparatus) Next, an electrophoresis apparatus using the fluidic device 1C (see FIG. 6) of this embodiment will be described. FIG. 8 is a configuration diagram of a capillary electrophoresis apparatus Ap (hereinafter simply referred to as "electrophoresis apparatus Ap"), which is an example of an analytical apparatus. This electrophoresis apparatus Ap is used as a DNA sequencer, a DNA fragment analyzer, or the like. As shown in FIG. 8, the electrophoresis apparatus Ap is mainly configured to include the fluidic device 1C, a capillary 26, a reagent bottle 31, a container 32, a container 33, a high-voltage power supply 50, and a laser light source 60.

[0060] The capillary 26 has a sample injection end 26a and a capillary body 26b having the sample injection end 26a at one end. The other end of the capillary body 26b is immersed in a reagent (described below) filled in a container 32. The sample injection end 26a is attached to a recess 25 of the fluidic device 1C. A negative electrode 52 is disposed in the container 32. The reagent bottle 31 is attached to one end 21g of the flow path 23C4 of the fluidic device 1C via a valve 41. The reagent bottle 31 in this embodiment is assumed to store a buffer gel as a reagent.

[0061] The container 33 is attached to one end 21h of the flow path 23C1 via a valve 43. The container 33 is filled with the reagent from the reagent bottle 31, as will be described later. A positive electrode 53 is disposed in the container 33. A high-voltage power supply 50 applies a voltage between the negative electrode 52 and the positive electrode 53. A laser light source 60 irradiates a laser beam 61 onto a predetermined position 62 on the capillary body 26b.

[0062] Next, the operation of the electrophoresis apparatus Ap will be described mainly with reference to Fig. 8. The fluidic device 1C of this electrophoresis apparatus Ap functions as a liquid delivery device for the reagent stored in the reagent bottle 31. A motor-driven plunger pump (not shown) is attached to the opening of the recess 24 of the fluidic device 1C.

[0063] In this electrophoresis apparatus Ap, when the sample injection end 26a is closed, the valve 43 is closed, the valve 41 is opened, and the plunger pump is driven to suck in, the reagent in the reagent bottle 31 fills the recess 24. Next, when the valve 41 is closed, the sample injection end 26a is opened, and the plunger pump is driven to push out, the reagent in the recess 24 is transferred to the container 32 via the capillary 26. By repeating this operation as necessary, the container 32 is filled with the reagent to the extent that the tip of the capillary 26 is immersed. The negative electrode 52 is immersed in the reagent. The hollow portion of the capillary 26 is then filled entirely with the reagent.

[0064] Next, in this electrophoresis apparatus Ap, when the sample injection end 26a is closed, the valve 43 is closed, and the valve 41 is opened, and the plunger pump is driven to suck in, the reagent in the reagent bottle 31 fills the recess 24. Next, when the valve 41 is closed, the valve 43 is opened, and the plunger pump is driven to push out, the reagent in the recess 24 is transferred via the flow paths 23C3, 23C2, and 23C1 and the capillary 26 to the container 33. By repeating this operation as necessary, at least the container 33, the flow paths 23C1 and 23C2, and the recess 25 are filled with the reagent. Then, by opening the valve 43 and the sample injection end 26a, an electrophoresis path is formed between the negative electrode 52 and the positive electrode 53 via the reagent.

[0065] In an analysis method using this electrophoresis apparatus Ap, a sample containing multiple types of components (such as DNA fragments) labeled with multiple types of fluorescent substances is injected into the sample injection end 26 a. When a voltage is then applied between the negative electrode 52 and the positive electrode 53, the negatively charged components (such as DNA fragments) contained in the sample are electrophoresed through the capillary body 26 b from the sample injection end 26 a toward the container 32.

[0066] Due to differences in mobility due to electrophoresis, the multiple types of components contained in the sample are gradually separated. A laser beam 61 emitted from a laser light source 60 is irradiated at position 62, where the components have electrophoresed a certain distance on the capillary body 26b. The laser beam 61 stimulates the emission of fluorescence from the multiple types of fluorophores labeled on the components that pass sequentially through position 62. The fluorescence that changes over time due to electrophoresis is measured by a multicolor detection device (not shown) that detects light in multiple wavelength bands.

[0067] Next, the effects of the fluidic device 1C of this embodiment, its manufacturing method, and the electrophoresis apparatus using the same will be described. The fluidic device 1C of this embodiment is a fluidic device 1C made of resin and mounted on an analytical apparatus, and has a plurality of flow paths 23C1, 23C2, 23C3, and 23C4 therein, each of which has an aspect ratio (length to diameter) of 10 or more and a circular tubular cross-sectional shape, and the arithmetic mean roughness of the inner wall surfaces of the flow paths 23C1, 23C2, 23C3, and 23C4 is 0.5 μm or less and a standard deviation of 0.1 μm or less.

[0068] This fluidic device 1C has an internal flow path 23C that has an aspect ratio (length to diameter) of 10 or more and a tubular cross-sectional shape with a circular cross section, and the arithmetic mean roughness of the inner wall surface of the flow path 23C is 0.5 μm or less and a standard deviation of 0.1 μm or less, thereby achieving the same effects as the fluidic device 1A of the first embodiment. Furthermore, the fluidic device 1C has multiple internal flow paths 23C1, 23C2, 23C3, and 23C4, which allows for diversification of fluid flow paths within the fluidic device 1C.

[0069] In addition, in such a fluidic device 1C, the resin is preferably an acrylic resin. This fluidic device 1C provides excellent moldability for the resin substrate 11 (resin block) that serves as the base, and facilitates machining for forming the through-holes 20C in the resin substrate 11. This fluidic device 1C also provides a wide range of organic solvents to be introduced into the through-holes 20C.

[0070] In addition, in such a fluidic device 1C, the inner wall surface of the flow channel 23C is made of SiO ２ According to this fluidic device 1C, the surface energy of the inner wall surface of the flow channel 23C is increased, so that adhesion of air bubbles can be more reliably suppressed.

[0071] In addition, in such a fluidic device 1C, the inner wall surfaces of the recesses 24 and 25 are made of SiO ２ According to this fluidic device 1C, the surface energy of the inner wall surfaces of the recesses 24 and 25 is increased, so that adhesion of air bubbles can be more reliably suppressed.

[0072] In such a fluid device 1C, the flow paths 23C are formed by holes penetrating the resin substrate 11 (resin block), and the resin substrate 11 (resin block) has recesses 24 and 25 that open to the surface of the resin substrate 11 (resin block), and at least two of the plurality of flow paths 23C, i.e., flow path 23C2 and flow path 23C3, communicate with each other via the recess 25. Furthermore, flow path 23C3 and flow path 23C4 communicate with each other via the recess 24.

[0073] According to this fluidic device 1C, it is possible to ensure a longer flow path length within the resin substrate 11 (resin block), thereby extending the residence time of the fluid within the resin substrate 11 (resin block).

[0074] In addition, in this fluidic device 1C, a plurality of recesses (recesses 24, 25) are formed in the resin substrate 11 (resin block). According to this fluidic device 1C, various parts and devices such as pumps and capillaries can be easily attached via the recesses 24, 25.

[0075] A manufacturing method for such a fluidic device 1C includes the steps of preparing a resin substrate 11 (resin block), forming a through-hole 20C having a circular cross-section in the resin substrate 11 (resin block), and introducing vapor of an organic solvent into the through-hole 20C while suctioning from one end 21e, 21f, and 21g of the through-hole 20C. In this manufacturing method, the through-hole 20C is formed by machining the resin substrate 11 (resin block). In this manufacturing method, recesses 24 and 25 are formed in the resin substrate 11 using a drill or the like. Then, the through-hole 20C having a circular cross-section is formed by machining. Then, drill marks are formed on the inner wall surfaces of the through-hole 20C and the recesses 24 and 25. When a fluid is passed through the through-hole 20C in this state, air bubbles are likely to adhere to the inner wall surfaces.

[0076] Therefore, in the manufacturing method of this embodiment, the organic solvent vapor is introduced into the through-hole 20C while suction is performed from the one ends 21e, 21f, and 21g of the through-hole 20C. The suction from the one ends 21e and 21f is performed through the recess 25. The organic solvent vapor is introduced into the through-holes 20C3 and 20C4 through the recess 24. This dissolves the inner wall surfaces of the flow path 23C and the recesses 24 and 25, making them smooth. This manufacturing method allows the manufacture of a fluidic device 1C having a flow path 23C with an inner wall surface having minimal surface roughness.

[0077] In this manufacturing method, it is preferable that the resin constituting the resin block is an acrylic resin and the organic solvent is dichloromethane. This manufacturing method makes it possible to efficiently form flow paths 23C in resin substrate 11 (resin block) having an inner wall surface roughness with an arithmetic mean of 0.5 μm or less and a standard deviation of 0.1 μm or less.

[0078] In addition, in such a manufacturing method, after the flow path 23C is formed by performing a step of introducing vapor of an organic solvent into the through hole 20C, SiO ２ According to this manufacturing method, it is preferable to further include a step of forming a SiO ２ The film allows the flow path 23C to have a large surface energy, which more reliably prevents air bubbles from adhering to the flow path 23C of the fluidic device 1C.

[0079] The electrophoresis apparatus Ap of this embodiment also includes a fluidic device 1C, in which flow paths 23C1 and 23C2 form part of the electrophoresis flow path. In an electrophoresis apparatus Ap using a machined resin substrate 11 (resin block) as shown in the diagram of reference numeral 702 in FIG. 7 , air bubbles mixed in when aspirating a reagent adhere to the inner wall surface of the through-hole 20C, which serves as the flow path. This inhibits electrophoresis through the through-hole 20C. Furthermore, if the air bubbles are large and block the through-hole 20C, there is a risk of damaging the negative electrode 52 and the positive electrode 53.

[0080] In contrast, in the fluidic device 1C used in the electrophoresis apparatus Ap of this embodiment, bubbles do not adhere to the inner wall surface of the flow channel 23C. Even if the bubbles are large, they are pushed out into the containers 32 and 33. In addition, the inner wall surfaces of the flow channel 23C and the recesses 24 and 25 are not covered with SiO ２ An electrophoresis apparatus Ap using a membrane-equipped fluidic device 1C can increase the surface energy of the inner wall surface thereof, thereby more effectively suppressing the adhesion of air bubbles, thereby enabling the electrophoresis apparatus Ap to perform even better electrophoresis.

[0081] Next, the results of verifying the effects of the fluidic device according to the embodiment of the present invention will be described. (Example 1) In Example 1, the fluidic device 1B shown in FIG. 4 was fabricated using acrylic resin. First, a curved through-hole 20B (see FIG. 5, reference numeral 502) was formed in a prepared resin substrate 11 (see FIG. 5, reference numeral 501) by machining using a drill. The through-hole 20B had a length of 50 mm and an inner diameter of 0.8 mm. The aspect ratio (length / inner diameter) of this through-hole 20B was 62.5.

[0082] Next, as shown in FIG. 5, 503, suction was applied from one end 21c of the through-hole 20B while dichloromethane vapor was introduced from the other end 21d. This resulted in a fluidic device 1B (see FIG. 5, 504) having a flow path 23B (see FIG. 5, 504) with a smoothed inner wall surface. The length of the flow path 23B from the end that served as the vapor inlet and the roughness of the inner wall surface at a position corresponding to that length were measured using arithmetic mean roughness (Ra) in accordance with ISO 4287-1997. The results are shown in the graph of FIG. 9.

[0083] The horizontal axis in FIG. 9 represents the position of one end of flow path 23B, i.e., the dichloromethane vapor inlet end, as 0 mm, and the position of the other end of flow path 23B as 50 mm. The vertical axis in FIG. 9 represents the measured surface roughness [μm] (arithmetic mean roughness (Ra)) of the inner wall surface. In FIG. 9, the surface roughness [μm] of Example 1, indicated by circles, is generally concentrated at 0.1 μm or less throughout the entire longitudinal length of flow path 23B. Although the maximum surface roughness [μm] (0.4 μm) is observed in a portion of the length of 5 mm or less corresponding to the dichloromethane vapor inlet end, the surface roughness [μm] is 0.5 μm or less. Furthermore, the standard deviation of the roughness of the inner wall surface throughout the entire longitudinal length of flow path 23B was 0.1 μm or less in root mean square height (Sq) according to ISO 25178.

[0084] Comparative Example 1 In Comparative Example 1, a resin substrate 11 having a through-hole 20B formed therein, as shown in the diagram of reference numeral 502 in FIG. 5, was exposed to dichloromethane vapor in a bath without being suctioned from one end 21 of the through-hole 20B, thereby obtaining a fluidic device. The surface roughness [μm] of the inner wall surface of the flow path of this fluidic device was measured in the same manner as in Example 1. The results are shown by square marks in the graph of FIG. 9. As shown in FIG. 9, the surface roughness [μm] of the flow path in the fluidic device of Comparative Example 1 was 0.5 μm or more throughout the entire longitudinal direction. In other words, the inner wall surface of the flow path was not smoothed. Furthermore, the root-mean-square height (Sq) according to ISO 25178 also exceeded 0.1 μm.

[0085] Comparative Example 2 In Comparative Example 2, a resin substrate 11 having a through-hole 20B formed therein, as shown in the diagram of reference numeral 502 in FIG. 5, was subjected to reaming of the inner wall surface of the through-hole 20B. In Comparative Example 2, a fluidic device was fabricated by only reaming the through-hole 20B without exposing the resin substrate 11 to dichloromethane vapor. The surface roughness [μm] of the inner wall surface of the flow path of this fluidic device was measured in the same manner as in Example 1. The results are shown by triangles in the graph of FIG. 9. As shown in FIG. 9, although the surface roughness [μm] of the flow path in the fluidic device of Comparative Example 2 was 0.5 μm or less in some locations, the surface roughness [μm] varied significantly, with a standard deviation of 0.2 μm or more. The surface roughness and standard deviation varied significantly, particularly from a length of 8 mm, where the aspect ratio exceeded 10.

[0086] (Evaluation Results) It was confirmed that the fluidic device of Comparative Example 1 was fabricated by simply exposing the resin substrate 11 to dichloromethane vapor, and therefore the inner wall surface of the through-hole 20B could not be smoothed. Furthermore, it was confirmed that the fluidic device of Comparative Example 1 had a large variation in surface roughness [μm] because the flow path was formed solely by mechanical polishing of the through-hole 20B. In contrast, it was verified that the fluidic device 1B of Example 1 of the present invention (see the diagram indicated by reference numeral 504 in FIG. 5 ) had an arithmetic mean roughness of the inner wall surface of the flow path 23B of 0.5 μm or less and a standard deviation of 0.1 μm or less by suctioning from one end of the through-hole while introducing organic solvent vapor from the other end.

[0087] Although the embodiments of the present invention have been described above, the present invention is not limited to the above embodiments, and various modifications are possible within the scope of the present invention. In the first to third embodiments, the fluidic devices 1A, 1B, and 1C were described in which the through-holes 20A, 20B, and 20C were formed in the resin substrate 11 (resin block) by machining. However, the fluidic devices 1A, 1B, and 1C having the through-holes 20A, 20B, and 20C can be fabricated using a 3D printer. Furthermore, the electrophoresis device Ap of this embodiment was described as using the flow path 23C of the fluidic device 1C of the third embodiment as a part of the flow path for electrophoresis. However, the flow paths 23A and 23B of the fluidic devices 1A and 1B can also be used as a part of the flow path for electrophoresis.

[0088] 1A, 1B, 1C Fluidic device 20A, 20B, 20C Through-hole 23A, 23B, 23C Flow path 11 Resin substrate (resin block) 24, 25 Recess Ap Electrophoresis device

Claims

1. A resin fluid device to be mounted on an analytical instrument, the fluid device having an internal flow path that has an aspect ratio (the ratio of length to diameter) of 10 or more and a tubular shape with a circular cross-section, the arithmetic mean roughness of the inner wall surface of the flow path being 0.5 μm or less and the standard deviation being 0.1 μm or less.

2. The fluidic device according to claim 1, wherein the resin is an acrylic resin.

3. The inner wall surface of the flow path is made of SiO ２ 2. The fluidic device according to claim 1, which is covered with a membrane.

4. A resin fluid device to be mounted on an analytical instrument, the fluid device having multiple internal flow paths with an aspect ratio (length to diameter) of 10 or more and a circular tubular cross-sectional shape, the arithmetic mean roughness of the inner wall surface of the flow paths being 0.5 μm or less and the standard deviation being 0.1 μm or less.

5. The fluidic device according to claim 4, wherein the resin is an acrylic resin.

6. The inner wall surface of the flow path is made of SiO ２ 5. The fluidic device according to claim 4, which is covered with a membrane.

7. The fluid device described in claim 4, characterized in that the flow paths are formed by holes penetrating a resin block, the resin block has a recess opening into a surface of the resin block, and at least two of the multiple flow paths are connected via the recess.

8. The fluid device according to claim 7, wherein a plurality of said recesses are formed in said resin block.

9. An electrophoresis apparatus comprising the fluidic device according to claim 1 or 4, wherein the flow path in the fluidic device constitutes a part of a flow path for electrophoresis.

10. An electrophoretic device according to claim 9, wherein said resin is an acrylic resin.

11. The inner wall surface of the flow path is made of SiO ２ 10. An electrophoretic device according to claim 9, characterized in that it is covered with a membrane.

12. The inner wall surface of the recess is made of SiO ２ 8. An electrophoretic device according to claim 7, characterized in that it is covered with a membrane.

13. A method for manufacturing a fluid device having an internal flow path that has an aspect ratio, which is the ratio of length to diameter, of 10 or more and a tubular cross-sectional shape with a circular cross-section, and the arithmetic mean roughness of the inner wall surface of the flow path is 0.5 μm or less and a standard deviation of 0.1 μm or less, the method comprising the steps of: forming a through hole having a circular cross-sectional shape in a resin block; and sucking from one end of the through hole while introducing organic solvent vapor from the other end.

14. The method for manufacturing a fluidic device according to claim 13, wherein the through holes are formed by machining the resin block.

15. The method for manufacturing a fluidic device according to claim 13, characterized in that the resin constituting the resin block is an acrylic resin, and the organic solvent is dichloromethane.

16. After the step of introducing the vapor of the organic solvent into the through hole, a SiO ２ The method for producing a fluidic device according to claim 13, further comprising the step of forming a membrane.

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