JP6729027B2 - Micro channel chip - Google Patents

Description

The present invention relates to a microchannel chip. More specifically, it relates to a microchannel chip capable of separating a specific component such as a plasma component from a sample such as blood.

Bilirubin, which is the main component of the color of serum (plasma), is produced mainly by the breakdown of hemoglobin in red blood cells. When this bilirubin increases in the body, the skin of the whole body becomes yellow and becomes jaundice. In general, most jaundice (about 90% of newborns) that appear in the neonatal period are physiological symptoms and disappear spontaneously in 3 to 5 days after birth. However, pathological jaundice that exceeds the range of physiological jaundice (about 20% of newborns with jaundice) progresses to “nuclear jaundice” that causes central nervous system disorders, and causes severe cerebral palsy, deafness, intellectual disability, etc. It may result in serious aftereffects and may lead to death. In order to prevent this, NICU (neonatal intensive care unit) and obstetrics screen newborns with jaundice by quantitatively measuring blood bilirubin and screening them based on total bilirubin concentration. For that, phototherapy is performed. A colorimetric method is mainly adopted as a method for quantitatively measuring bilirubin.

As a method for quantitatively measuring bilirubin by a colorimetric method, a two-wavelength photometric method is known in which the concentration of bilirubin contained in plasma is measured by measuring the absorbance of light at two different wavelengths in plasma. (See, for example, Non-Patent Document 1).
The method for quantitatively measuring bilirubin by the two-wavelength photometry will be specifically described as follows.

Plasma extracted from blood may contain hemolyzed hemoglobin (hemoglobin leaked from damaged red blood cells) in addition to bilirubin. In such a case, when the spectral absorption curve of plasma is measured, as shown in FIG. 15, the absorption curve of plasma becomes an absorption curve in which the absorption curve of bilirubin, hemolytic hemoglobin and the absorption curve are combined. In FIG. 15, the solid line is the absorption curve of extracted plasma, the broken line is the absorption curve of bilirubin, and the dashed-dotted line is the absorption curve of hemolyzed hemoglobin.

As can be understood from FIG. 15, the absorption peak due to bilirubin is a wavelength of 455 nm. However, the absorption by plasma at a wavelength of 455 nm includes the absorption by hemolyzed hemoglobin in addition to the absorption by bilirubin. Therefore, the absorbance B ₁ of plasma at a wavelength of 455 nm is the absorbance B _{2 of} bilirubin and the absorbance of hemolyzed hemoglobin. It is the sum of H ₂ . Therefore, the concentration of bilirubin cannot be calculated from the absorbance B ₁ alone.
On the other hand, in the absorption curve of plasma, focusing on a wavelength of 575 nm in which there is no absorption by bilirubin but only absorption by hemolyzed hemoglobin, the value of absorbance H ₁ of plasma is similar to the value of absorbance H ₂ of hemolyzed hemoglobin at a wavelength of 455 nm. ing.
Therefore, by subtracting the value of the absorbance H _{1 at} the wavelength of 575 nm from the value of the absorbance B _{1 at} the wavelength of 455 nm, a value close to the value of the absorbance B ₂ of bilirubin is obtained, and the concentration of bilirubin is determined from this value. Is possible.

Further, in order to measure the concentration of bilirubin in blood, it is necessary to extract plasma containing bilirubin from blood. As a method of extracting plasma from blood, there is known a method of separating plasma and blood cells in blood by centrifuging blood enclosed in a capillary tube (see, for example, Patent Document 1).

Yoshisuke Ogawa, "Basics of Colorimetric Analyzer", Biological Sample Analysis, Biological Sample Analytical Science Society, 2013, Vol. 36, No. 3, p. 273-280

JP-A-6-43158

However, when centrifugation is used to separate plasma from blood, a relatively large amount of blood is required, and since a centrifuge is used, it is necessary to construct a large device. , There is a problem. Therefore, there is a demand for means capable of separating plasma components from a trace amount of blood without using centrifugation.

Therefore, an object of the present invention is to separate a specific component from a trace amount of a sample without adding a kinematic action such as a centrifugal force from the outside, and a necessary amount of the specific component was filled in a measurement unit. It is to provide a microchannel chip that can obtain the state in a short time.

The microchannel chip of the present invention comprises a first channel for circulating a liquid sample, a plurality of second channels for separating a specific component from the sample flowing through the first channel, and from the sample. Consisting of a plate-shaped body having a measuring part filled with the separated specific component therein,
Each of the plurality of second flow paths is a component to be excluded from the sample, which is opened in the flow path forming surface forming the first flow path and communicates with the first flow path and is connected to the measurement unit. Do a groove having a width of dimension capable of blocking the entry for the second channel Ri,
The measurement unit has a wedge-shaped space in which the gap gradually decreases in one direction of the surface direction, and a constant volume space having substantially the same spatial shape in the one direction continuous with the wedge-shaped space. Cage,
An angle formed by two continuous constant volume space forming surfaces that are represented in a cross section perpendicular to the one direction of the constant volume space is γ, and a pair of mutually facing sides that are represented in a side view from the surface direction of the wedge-shaped space. When the angle formed by the wedge-shaped space forming surface is α, the wedge-shaped space has a space shape that satisfies the relationship of α<γ .

Further, in the microchannel chip of the present invention, when the angle formed by a pair of wedge-shaped space forming surfaces opposed to each other when viewed in a plan view from the thickness direction of the wedge-shaped space is β, the wedge-shaped space Preferably has a spatial shape that satisfies the relationship β<γ.

Furthermore, in the microchannel chip of the present invention, it is preferable that the width of the first channel is 10 μm or more and 1000 μm or less and the width of the second channel is 0.1 μm or more and 1.2 μm or less.
Further, it is preferable that the measurement section has a measurement region having a constant dimension in the thickness direction, and the dimension in the thickness direction of the measurement region is 10 to 1000 μm.

Furthermore, in the microchannel chip of the present invention, it is preferable that the hydrophilicity of the channel forming surface forming the second channel is lower than the hydrophilicity of the channel forming surface forming the first channel.

According to the micro-channel chip of the present invention, the second channel has a width capable of inhibiting the invasion of the components to be excluded in the sample flowing through the first channel into the second channel, It is possible to separate a specific component from a specimen without applying a kinematic effect such as centrifugal force.

In addition, since a part of the measurement unit is formed by a wedge-shaped space having a specific space shape, a specific component that is separated by the second flow channel and flows into the measurement unit is wedge-shaped. It is possible to concentrate in the narrow direction of the wedge-shaped space by the capillary force of the space. Therefore, it is possible to obtain a state in which the required amount of the specific component is filled in the measurement unit in a short time.

Furthermore, since the hydrophilicity of the flow path forming surface forming the second flow path is lower than the hydrophilicity of the flow path forming surface forming the first flow path, the capillary force of the second flow path is reduced. It can be prevented from becoming too high. Therefore, when the sample is blood, it is possible to reliably avoid hemolysis of blood cells, which is a component to be excluded.

It is a top view which shows the structure in an example of the microchannel chip of this invention. It is explanatory drawing which shows the area|region enclosed by the dashed-two dotted line in FIG. 1, (a) is a top view, (b) is a side view. It is an AA cross-section end view in FIG. It is a BB cross-section end view in FIG. It is explanatory drawing which shows roughly the space shape of a measurement part, Comprising: (a) Perspective view, (b) Plan view seen from z direction, (c) Sectional view by yz plane of constant volume space, (d)y. It is the side view seen from the direction. It is a figure for demonstrating the separation function of the sample (blood) by a 2nd flow path. It is explanatory drawing which shows schematically the state which the specific component isolate|separated from the test substance flowed into the measurement part. It is a top view which shows the structure of the principal part in the other example of the microchannel chip of this invention. It is a top view which shows the structure in the further another example of the microchannel chip of this invention. It is explanatory drawing which shows roughly the spatial shape of each of a 1st flow path, a 2nd flow path, and a measurement part in the other example of the micro flow path chip of this invention. It is explanatory drawing which shows roughly the structure in an example of the sample concentration measuring apparatus using the microchannel chip of this invention. It is explanatory drawing which shows roughly the structure in the other example of the sample concentration measuring apparatus using the microchannel chip of this invention. It is a figure which is obtained about each of the some microchannel chip AD produced in the Example, and shows the relationship between the light absorbency (hemolysis intensity|strength) of hemolyzed hemoglobin and the hydrophilicity of the second channel. It is a figure which shows the time-dependent change of the storage length with respect to the measurement part of the test fluid about the microchannel chip A and the microchannel chip for comparison which were produced in the Example. It is a graph which shows each spectral absorption spectrum of a plasma component, bilirubin, and hemolytic hemoglobin.

Hereinafter, embodiments of the microchannel chip of the present invention will be described.
FIG. 1 is a plan view showing the configuration of an example of the microchannel chip of the present invention. 2A and 2B are explanatory views showing a region surrounded by an alternate long and two short dashes line in FIG. 1, in which FIG. 2A is a plan view and FIG. 2B is a side view. 3 is an end view of the AA cross section in FIG. 2A, and FIG. 4 is an end view of the BB cross section in FIG. 2A.
The micro-channel chip 10 includes a first channel 20 for circulating a liquid sample, and a plurality of second channels 25 for separating and extracting a specific component from the sample circulating in the first channel 20, It has a chip base 11 made of a plate-shaped body having therein a measurement unit 30 filled with a specific component separated from a sample.

In the illustrated example, the chip substrate 11 is configured by bonding the first substrate 12 and the second substrate 15, and the first channel 20, the second channel 25, and the measuring unit 30 have the thickness of the chip substrate 11. It is formed two-dimensionally along a plane perpendicular to the direction.
The measuring section 30 is formed in a state of extending in one direction of a surface direction perpendicular to the thickness direction of the chip base body 11, and is connected to the second discharging section 28 via the third flow path 27.
The first flow path 20 has linear flow path portions 20a and 20b extending along the measurement unit 30 at positions on both sides of the measurement unit 30. An upstream end of the first flow path 20 in the sample circulation direction is connected to a sample storage unit 22 that stores the sample introduced from the sample introduction unit 21. The downstream end of the first flow path 20 in the sample circulation direction is connected to the first discharge part 23.
Each of the plurality of second flow paths 25 is opened in the flow path forming surface forming the first flow path 20 and communicates with the first flow path 20 and is connected to the space forming the measurement unit 30. It consists of a groove extending perpendicular to the passage 20. The second flow passage 25 has an upstream end opening to the bottom wall surface 20c of the first flow passage 20, and the opening of the second flow passage 25 is formed to extend over the entire width direction of the first flow passage 20, for example. ing.
The thickness of each of the first substrate 12 and the second substrate 15 is not particularly limited, but is, for example, 0.1 mm or more and 5.0 mm or less.

In the illustrated example, the first flow path 20 is formed by being partitioned by the inner wall surface of the first flow path groove 13 a formed in the first substrate 12 and the second substrate 15. The second flow path 25 is formed by being partitioned by the inner wall surface of the second flow path groove 16 formed in the second substrate 15 and the first substrate 12. The measurement unit 30 is formed by being partitioned by the inner wall surface of the measurement unit recess 13 b formed on the first substrate 12 and the second substrate 15. The first flow channel groove 13a, the second flow channel groove 16 and the measuring section recess 13b may all be formed on either one of the first substrate 12 and the second substrate 15.

The first flow path 20 has a width that allows a liquid sample (eg, blood) to flow therethrough. In the present invention, the “width” of the flow channel means the smallest width of the flow channel in a cross section of the flow channel perpendicular to the direction in which the flow channel extends. In the first channel 20 and the second channel 25 of the illustrated example, the width of the microchannel chip 10 in the thickness direction is the smallest width.
The width of such a first flow path 20 is preferably 10 μm or more and 1000 μm or less, and more preferably 50 μm or more and 100 μm or less. When the width of the first flow path 20 is too small, the flow rate of the sample in the first flow path 20 increases due to the increase in the flow path resistance, and a specific component (for example, plasma component) to the second flow path 25 is reduced. There is a risk that the supply amount of On the other hand, if the width of the first flow path 20 is excessively large, the amount of required sample may increase. Further, since the capillary force becomes small, the flow velocity of the sample flowing through the first flow path 20 becomes small, and it may take a considerably long time for the specific component to reach the measurement unit 30.
The length from the upstream end of the first flow path 20 to the branch point with the second flow path 25 is not particularly limited, but is, for example, 10 mm or more and 100 mm or less.

The second channel 25 separates a specific component (eg, plasma component) from a sample (eg, blood) flowing through the first channel 20 and introduces a component (eg, blood cell) to be excluded into the second channel 25. It has a width that can be blocked.
The width of such a second flow path 25 is preferably 0.1 μm or more and 1.2 μm or less, and more preferably 1 μm or more and 1.2 μm or less. If the width of the second flow path 25 is too small, the amount of the specific component that can be supplied to the measurement unit 30 decreases, and it may take a considerably long time to extract the specific component. On the other hand, when the width of the second flow path 25 is excessively large, components other than the specific component (for example, blood cell components such as red blood cells) in the sample may be mixed and the separation function may not be exhibited.
The length of the second flow path 25 is not particularly limited, but is, for example, 0.1 mm or more and 1 mm or less.
Further, the number of the second flow paths 25 is, for example, 100 or more and 10000 or less.

In the measurement unit 30, at least a part of the space forming the measurement unit 30 is formed by a wedge-shaped space in which the gap gradually decreases in one direction.

In the illustrated example, one end portion of the measuring unit 30 in the extending direction of the measuring unit 30 is formed by a wedge-shaped space. That is, as shown in FIG. 5, the measuring unit 30 includes a wedge-shaped space 35 and a constant volume space 31 continuous with the wedge-shaped space 35.
In the following, the spatial shape of the measurement unit 30 is defined by defining xyz orthogonal coordinates in which the direction in which the wedge-shaped space 35 (measurement unit 30) extends is the “x direction” and the thickness direction of the chip base body 11 is the “z direction”. This will be specifically described.

The constant volume space 31 in the measurement unit 30 has substantially the same space shape in the x direction, and the cross-sectional shape of the yz cross section is rectangular. The angle γ formed by two continuous constant volume space forming surfaces represented in the yz cross section of the constant volume space 31 is, for example, 45° or more and 90° or less.
In the illustrated example, the constant volume space 31 is formed by an upper bottom surface 30a and a lower bottom surface 30b each extending along the xy plane, and a pair of constant volume space forming surfaces 32a, 32b inclined with respect to the lower bottom surface 30b. The yz cross section has a trapezoidal space shape. Then, the angles γ1 and γ2 formed by the pair of constant volume space forming surfaces 32a and 32b facing each other in the y direction represented in the yz cross section of the constant volume space 31 with respect to the lower bottom surface 30b along the xy plane are, for example, 45°. The angle is 90° or less. γ1 and γ2 may have the same size or different sizes.

The wedge-shaped space 35 has a pair of wedge-shaped space forming surfaces that face each other in the z-direction when viewed in a plan view from the y direction and has a wedge shape, and the wedge-shaped space 35 is viewed in a plan view from the z-direction. It is preferable that the pair of wedge-shaped space forming surfaces facing each other in the direction has a space shape having a wedge-shaped portion.
Specifically, when the angle formed by the pair of wedge-shaped space forming surfaces in plan view from the y direction (hereinafter referred to as the “tip inclination angle of the wedge-shaped space”) is α, the wedge-shaped space 35. Preferably has a spatial shape that satisfies the relationships α<γ1 and α<γ2. Further, when the angle formed by the pair of wedge-shaped space forming surfaces in plan view from the z direction (hereinafter, referred to as “opening angle of wedge-shaped space”) is β, the wedge-shaped space 35 is β<. It is preferable to have a spatial shape having a spatial shape that satisfies the relationship of γ1 and β<γ2.

In the illustrated example, the wedge-shaped spaces 35 form a pair of wedge-shaped spaces inclined with respect to the lower bottom surface 30b, which are close to each other toward the one end side in the x direction and the upper bottom surface 30a and the lower bottom surface 30b along the xy plane. It is formed by the surfaces 36a and 36b.
Then, as shown in FIG. 5D, the tip inclination angle of the wedge-shaped space 35 formed by the ridgeline C of the pair of wedge-shaped space forming surfaces 36a and 36b and the lower bottom surface 30b when viewed in plan from the y direction. α is smaller than the inclination angles γ1 and γ2 with respect to the lower bottom surface 30b of the constant volume space forming surfaces 32a and 32b. Further, as shown in FIG. 5B, the opening angle β of the wedge-shaped space 35 formed by the pair of wedge-shaped space forming surfaces 36a and 36b when viewed in plan from the z direction is equal to the constant volume space forming surface 32a. , 32b are smaller than the inclination angles γ1 and γ2 with respect to the lower bottom surface 30b.
The space shape of the wedge-shaped space 35 may be, for example, a quadrangular pyramid shape.

The opening angle α of the wedge-shaped space 35 is preferably 15° or more and 45° or less, for example. Further, the tip end inclination angle β of the wedge-shaped space 35 is preferably, for example, 5° or more and 45° or less.
The capillary force P due to the wedge-shaped space 35 is P=2Fcosα+(θ/R) or P=2Fcosβ+(θ/, where F is the surface tension, θ is the contact angle of the liquid, and R is the radius of curvature of the liquid surface. R). Therefore, the capillary force P is determined by the opening angle α of the wedge-shaped space or the tip inclination angle β of the wedge-shaped space.
Since the wedge-shaped space 35 has the space shape as described above, the specific component separated by the second flow path 25 and flowing into the measurement unit 30 is reliably stored preferentially in the narrow direction of the wedge-shaped space 35. Can be made.

Further, it is preferable that the wedge-shaped space 35 has a measurement region having a constant size in the y direction or the z direction.
In the illustrated example, the measurement region 38 having a constant size (thickness) in the z direction is formed in the wedge-shaped space 35 at the other end side in the x direction.
With such a configuration, in the concentration measurement based on the absorbance of the specific component to be described later, the optical path length can be set to a certain size, and thus the highly reliable concentration measurement of the specific component in the sample can be performed. It can be carried out.

In the above, the dimension D in the z direction in the constant volume space 31 of the measurement unit 30 and the measurement region 38 of the wedge-shaped space 35 is, for example, preferably 10 μm or more and 1000 μm or less, and more preferably 100 μm or more and 500 μm or less. If the dimension D is too small, it is not possible to secure an optical path length of a size required in the absorbance measurement described later, and thus it becomes impossible to measure the concentration of a specific component. On the other hand, if the dimension D is excessively large, the amount of required sample may increase. Further, since the capillary force becomes small, it may take a considerably long time for the specific component to reach the measurement unit 30.
Further, the dimension W1 in the surface direction (y direction) in the constant volume space 31 of the measurement unit 30 is preferably 100 μm or more and 1000 μm or less.

Thus, in the above-described microchannel chip 10, a channel forming surface (inner wall surface) forming the first channel 20 and a channel forming surface (inner wall surface) forming each of the second channels 25 and measurement. It is preferable that the measurement portion forming surface (the inner wall surface of the measurement portion 30) forming the portion 30 is subjected to a hydrophilic treatment. Specifically, the contact angle of water on the inner wall surface of each of the first flow path 20, the second flow path 25, and the measurement unit 30 is preferably less than 90°, and more preferably 50° or less.
Moreover, it is preferable that the hydrophilicity of the flow path forming surface forming the second flow path 25 is lower than the hydrophilicity of the flow path forming surface forming the first flow path 20. Specifically, the contact angle of water on the flow path forming surface forming the second flow path 25 is preferably 70° or more and less than 90° (weakly hydrophilic), and the flow path forming the first flow path 20. The contact angle of water on the formation surface is preferably 10° or less (strong hydrophilicity). When the inner wall surface of the second flow channel 25 has a high hydrophilicity, the width of the second flow channel 25 is narrow, so that the capillary force of the second flow channel 25 is reduced as shown in the results of Examples described later. When the sample is blood, blood cells, which are components to be excluded, are easily hemolyzed because the cells become too large.

As the method of hydrophilic treatment, for example, a method of forming a hydrophilic thin film, a method of surface treatment by irradiating vacuum ultraviolet rays, and the like can be used.
The hydrophilic thin film can be composed of, for example, a laminated film including a noble metal thin film and a self-assembled monomolecular film (SAM) formed of hydrophilic molecules on the noble metal thin film. Examples of the noble metal thin film include a platinum film and the like. Further, examples of the hydrophilic molecule include thiol thiol. The adjustment of hydrophilicity can be controlled by the thickness of the noble metal thin film. That is, by making the thickness of the noble metal thin film formed on the inner wall surface of the second flow path 25 smaller than the thickness of the noble metal thin film formed on the inner wall surface of the first flow path 20, the hydrophilic property of the inner wall surface of the second flow path 25 is reduced. Sex can be lowered.
In the case where the surface activation treatment is performed by irradiating vacuum ultraviolet rays, a xenon excimer lamp that emits vacuum ultraviolet rays having a central wavelength of 172 nm can be used as the ultraviolet light source. For example, when an example of the UV irradiation conditions for the inner wall surface of the first flow path groove 13a in the first substrate 12 and the surface of the second substrate 15 forming the first flow path 20 together with the inner wall surface is shown, the UV illuminance is 30 mW/ cm ² , irradiation time is 10 minutes. In addition, an example of ultraviolet irradiation conditions for the inner wall surface of the second flow path groove 16 formed in the second substrate 15 and the surface of the first substrate 12 that forms the second flow path 25 together with the inner wall surface will be described. The ultraviolet illuminance is 30 mW/cm ² , and the irradiation time is 1 minute.
Note that the inclination angle of the pair of inner wall surfaces facing each other in the x direction forming the second flow path 25 with respect to the bottom wall surface extending along the xy plane is partially changed, so that the second flow path 25 can be formed. The hydrophilicity can also be adjusted.

<Constituent material of chip substrate>
As a material forming the chip substrate 11 (first substrate 12 and second substrate 15), a material that can transmit light from a light source unit in a sample concentration measuring device described later, for example, a resin material can be used.
As the resin material, for example, acrylic resin, polystyrene resin, COP resin (cycloolefin polymer resin) or the like can be used, but it is preferable to use the resin composition shown below.

It is preferable that the resin composition used as the constituent material of the chip substrate 11 has a deflection temperature under load of 40° C. or higher and 100° C. or lower and a glass transition temperature of −40° C. or higher and −20° C. or lower.
Here, the deflection temperature under load and the glass transition temperature of the resin composition are those measured by the methods specified in JIS K7191 and JIS K7121.

Examples of such a resin composition include a polypropylene resin, a polymer block X which is incompatible with the polypropylene resin (hereinafter, simply referred to as “polymer block X”), and an elastomeric polymer block Y (hereinafter, simply referred to as “polymer block X”) containing a conjugated diene. A self-melting composition containing a hydrogenated derivative (hereinafter, referred to as "specific hydrogenated derivative") of a block copolymer (hereinafter, referred to as "specific block copolymer") composed of "polymer block Y"). It is preferable to use a resin composition having adhesiveness (hereinafter, referred to as “specific resin composition”).

<Polypropylene resin>
As the polypropylene resin, a homopolymer of propylene or a random copolymer of propylene and ethylene or an α-olefin other than propylene such as butene-1, hexene-1 can be used. Specifically, for example, commercially available "Microresico" (registered trademark) (manufactured by Richell Co., Ltd.) and the like can be used.

<Specific block copolymer>
The specific block copolymer may have one or more, preferably one or more and five or less polymer blocks X and polymer blocks Y, and a specific structure thereof is (XY) _n (however, n=1 to 5), a structure represented by X-Y-X, a structure represented by Y-X-Y, and the like.

<Polymer block X>
In the specific block copolymer, the polymer block X is not particularly limited as long as it is incompatible with the polypropylene resin, and for example, vinyl aromatic monomer (for example, styrene), ethylene or methacrylate (for example, methyl methacrylate) is polymerized. The polymer block thus obtained can be used. Specific examples of the polymer block X include polystyrene type and polyolefin type.

Examples of the polystyrene-based polymer block X include 1 selected from styrene, α-methylstyrene, o-methylstyrene, m-methylstyrene, p-methylstyrene, 2,4-dimethylstyrene, vinylnaphthalene, and vinylanthracene. Examples thereof include polymer blocks obtained by polymerizing one or more vinyl aromatic compounds.

Another example of the polyolefin-based polymer block X is a polymer block obtained by copolymerizing ethylene and an α-olefin having 3 to 10 carbon atoms. A non-conjugated diene may be conjugated and polymerized in this polymer block.
Specific examples of the α-olefin include propylene, 1-butene, 3-methyl-1-butene, 1-pentene, 4-methyl-1-pentene, 1-hexene, 1-pentene, 1-octene, 1-. For example, decene.
Specific examples of the non-conjugated diene include 1,4-hexadiene, 5-methyl-1,5-hexadiene, 1,4-octadiene, cyclohexadiene, cyclooctadiene, cyclopentadiene, 5-ethylidene-2-norbonel, 5-butylidene-2-norbonel, 2-isopropenyl-5-nerbornene and the like can be mentioned.
Specific examples of the polyolefin-based polymer block X include ethylene-propylene copolymer block, ethylene-1-butene copolymer block, ethylene-1-octene copolymer block, and ethylene-propylene-1,4-hexadiene copolymer block. Examples thereof include a polymer block and an ethylene-propylene-5-ethylidene-2-norbornene copolymer block.

In the specific block copolymer, the content rate of the polymer block X is, for example, 10% by mass or more and 20% by mass or less.

<Polymer block Y>
As the polymer block Y, as before hydrogenation, a polybutadiene block composed of a structural unit comprising at least one group selected from the group consisting of a 2-butene-1,4-diyl group and a vinylethylene group, Poly constituted by a structural unit composed of at least one group selected from the group consisting of a 2-methyl-2-butene-1,4-diyl group, an isopropenylethylene group and a 1-methyl-1-vinylethylene group. An isoprene block is mentioned.
Further, as the polymer block Y before hydrogenation, the isoprene unit is selected from the group consisting of a 2-methyl-2-butene-1,4-diyl group, an isopropenylethylene group and a 1-methyl-1-vinylethylene group. Examples thereof include an isoprene/butadiene copolymer block which is a structural unit composed of at least one kind of group, and a butadiene unit composed of a structural unit composed of a 2-butene-1,4-diyl group and/or a vinylethylene group. .. The arrangement of the isoprene-derived structural unit and the butadiene-derived structural unit in the isoprene/butadiene copolymer block may be any of random, block, and tapered block configurations.

Further, the polymer block Y may be formed by copolymerizing a vinyl aromatic compound. As such a polymer block Y, units derived from a vinyl aromatic compound are styrene, α-methylstyrene, o-methylstyrene, m-methylstyrene, p-methylstyrene, 2,4-dimethylstyrene, vinylnaphthalene. , A copolymer block in which the conjugated diene unit is a 2-butene-1,4-diyl group and/or a vinylethylene group, which is one kind of monomer unit selected from vinylanthracene and vinylanthracene. The arrangement of the structural unit derived from the vinyl aromatic compound and the structural unit derived from the conjugated diene may be any of random, block, and tapered block shapes.

<Specific hydrogenated derivative>
The specific hydrogenated derivative is obtained by hydrogenating the specific block copolymer described above. The state of hydrogenation in the specific hydrogenated derivative may be partial hydrogenation or complete hydrogenation.
As such a specific hydrogenated derivative, in the specific block copolymer before hydrogenation, the polymer block X is a polystyrene block and the polymer block Y is 1, 2 bonds, 3, 4 bonds and/or 1, Those which are 4-bond polyisoprene blocks, or those in which the polymer block X is a polystyrene block and the polymer block Y is a 1,2-bond and/or 1,4-bond polybutadiene block are readily available. is there.
Further, since the polystyrene block is hard to be compatible with the polypropylene resin, when a specific hydrogenated derivative having a high polystyrene block ratio is used, preparation of a specific resin composition (specific hydrogenated derivative and polypropylene type resin) is performed. Since it takes a long time to mix with the resin), it is preferable to sufficiently mix them in advance by making them into a master batch.

The above-described micro-channel chip 10 includes, for example, a first substrate 12 in which a first channel groove 13a for forming the first channel 20 and a measuring section recess 13b for forming the measuring section 30 are formed, In addition, it is possible to manufacture by manufacturing the second substrate 15 in which the second flow channel groove 16 for forming the second flow channel 25 is formed and bonding the first substrate and the second substrate.
For the first substrate 12 and the second substrate 15, for example, a mold for manufacturing a micro-channel chip is manufactured, and using the mold for manufacturing a micro-channel chip, for example, the above resin material is molded by an injection molding method. Can be manufactured by. The mold for manufacturing a microchannel chip is manufactured, for example, by anisotropically etching a silicon wafer, or by subjecting a photosensitive resin obtained by oblique exposure or a multi-step process to electroforming. can do.

In the micro-channel chip 10 described above, a liquid sample, for example, blood is introduced from the sample introducing section 21 to store the sample in the sample storing section 22. The sample stored in the sample storage unit 22 flows through the first flow path 20 due to a capillary phenomenon and reaches a branch point with the second flow path 25. Then, at this branch point, as shown in FIG. 6, a component having a size larger than the width of the second flow channel 25 in the sample (indicated by a hatched arrow in FIG. 6), for example, a blood cell component BC, Since the entry to the second flow path 25 is blocked, the first flow path 20 flows toward the downstream side (indicated by a solid arrow in FIG. 6 ). On the other hand, a specific component having a size smaller than the width of the second flow channel 25 in the sample, for example, a plasma component (indicated by a white arrow in FIG. 6) PL can enter the second flow channel 25. The second channel 25 flows through the second channel 25 by the capillary force and flows into the measurement unit 30. As shown in FIG. 7, the specific component PL that has flowed into the measurement unit 30 is wedge-shaped space along the inner wall surface forming the measurement unit 30 in the chip base 11 due to the capillary force of the wedge-shaped space 35 in the measurement unit 30. It flows in the narrow direction of 35. Therefore, the specific component PL is concentrated in the wedge-shaped space 35 and is preferentially filled from the wedge-shaped space 35.

As described above, according to the microchannel chip 10 described above, the second channel 25 separates and removes a specific component (eg, plasma component PL) from the sample (eg, blood) flowing through the first channel 20. Since it has a width that can prevent a component (for example, blood cell BC) to enter the second flow path 25, a trace amount of the sample can be obtained without externally applying a kinematic action such as centrifugal force. From which specific components can be separated.

Further, according to the micro-channel chip 10 described above, the specific component separated by the second channel 25 and flowing into the measurement unit 30 is narrowed in the narrow direction of the wedge-shaped space 35 by the capillary force of the wedge-shaped space 35. Can be focused on. That is, in the structure in which the spatial shape of the measurement unit 30 is, for example, a prismatic shape, the specific component flowing into the measurement unit 30 is present at the boundary between two continuous measurement unit formation surfaces (for example, the bottom surface and the side wall surface). Due to the generated capillary force, it is held at a position in the vicinity of the measurement portion formation surface. That is, since the specific component is gradually filled from the position in the vicinity of the measurement portion forming surface, for example, in order to fill the amount of the specific component required in the concentration measurement, the extraction amount of the specific component is It becomes huge and takes a long time. Further, the specific component reaches the discharge portion (second discharge portion 28) along the measurement portion forming surface, and hinders the discharge of the air in the measurement portion 30.
However, since the part of the space forming the measurement unit 30 is formed by the wedge-shaped space 35, the above-described microchannel chip 10 can efficiently extract the required amount of the specific component from the sample. Therefore, it is possible to obtain a state in which the optical path length (the thickness of the specific component filled in the measuring unit 30 is 100 μm, for example) required in the concentration measurement based on the absorbance described later is ensured in a short time.

Furthermore, according to the above-described microchannel chip 10, since the hydrophilicity of the channel forming surface forming the second channel 25 is lower than the hydrophilicity of the channel forming surface forming the first channel 20, By the capillary force of the two flow paths 25, it is possible to avoid hemolysis of blood cells, which are components to be excluded.

Although the embodiments of the microchannel chip of the present invention have been described above, the present invention is not limited to the above embodiments, and various modifications can be added.
For example, in the above-described microchannel chip, the second channel does not need to be formed over the entire area of the measuring section in the direction in which the measuring section extends, and for example, as shown in FIGS. 8(a) and 8(b). As shown, it may be configured to be formed only in the constant volume space 31 of the measurement unit 30. Even with such a configuration, the specific component that has flowed into the measurement unit 30 can be concentrated in the narrow direction of the wedge-shaped space 35. Further, the inner wall surface (wedge-shaped space forming surface) forming the wedge-shaped space in the chip base does not need to be a flat surface, and the inner surface is formed in a stepped shape as shown in FIG. 8B. Good. Furthermore, as shown in FIG. 9, the second flow channel 25 is formed only on one side of the measurement unit 30 in the plane direction, that is, a straight line positioned on the upstream side in the sample flow direction of the first flow channel 20. The second flow path 25 may be formed so as to connect the linear flow path portion 20a and the measurement unit 30 to each other. Furthermore, the second flow path may be open to any flow path forming surface (inner wall surface) forming the first flow path. For example, as shown in FIG. It may be opened to the side wall surface forming the passage 20.
Furthermore, in the above-mentioned micro-channel chip, a wedge-shaped space is formed at one end portion of the measuring portion extending in the surface direction of the chip substrate, but the spatial shape of the measuring portion is not particularly limited. However, the wedge-shaped space may be formed so as to extend in any direction of the plane direction, or may be formed so as to extend in the thickness direction.
Furthermore, the chip base body may be configured by bonding a plurality of substrates, and may be configured by three-dimensionally forming the first flow path, the second flow path, and the measurement unit.

Hereinafter, a sample concentration measuring device using the microchannel chip of the present invention will be described.
FIG. 11 is an explanatory diagram showing the configuration of an example of a sample concentration measuring device using the microchannel chip of the present invention.
This sample concentration measuring device is for measuring the concentration of bilirubin by separating plasma containing bilirubin, which is a test target component, from blood which is a liquid sample.

The inspection object measuring apparatus shown in FIG. 11 has the microchannel chip 10 having the configuration shown in FIGS. 1 to 5 and the microchannel chip 10 for the measurement region 38 in the measuring section 30 of the microchannel chip 10. A light source 40 that irradiates light in the thickness direction, an image capturing unit 50 that captures an image of a region including the measurement unit 30 in the microchannel chip 10, and an inspection target based on image data related to the image captured by the image capturing unit 50. And a control mechanism 60 having a function of calculating the concentration of the component.

On the optical path between the light source 40 and the micro-channel chip 10, an optical filter 45 that limits the wavelength range of the transmitted light is arranged. A lens 48 for collimating the incident light is arranged between the optical filter 45 and the microchannel chip 10. A lens 51 is arranged between the micro-channel chip 10 and the image pickup means 50 to magnify an optical image formed by the light emitted from the light source 40 and project it on the image pickup means 50. Further, the light source 40 is electrically connected to a power supply 41 that supplies electricity to the light source 40. The power source 41 is electrically connected to the control mechanism 60.

As the light source 40, a light source that emits light including a wavelength range necessary for measuring the concentration of the component to be inspected is used. In this example, a light source 40 that emits light including a wavelength range near 455 nm and a wavelength range near 575 nm necessary for measuring the concentration of bilirubin contained in plasma is used.
As a specific example of such a light source 40, one composed of two kinds of LED elements that emit light in different wavelength ranges, for example, an LED element having a peak emission wavelength of 450 nm and an LED element having a peak emission wavelength of 570 nm can be mentioned. To be

As the optical filter 45, a bandpass filter is used that limits the wavelength range of the transmitted light to the wavelength range necessary for measuring the concentration of the component to be inspected. In this example, as the optical filter 45, a multi-bandpass filter that limits the wavelength range of transmitted light to the wavelength range near 455 nm and the wavelength range near 575 nm necessary for measuring the concentration of bilirubin contained in plasma is used. Is used. The bandwidths of the wavelength region near 455 nm and the wavelength region near 575 nm that pass through the optical filter 45 are 10 nm or more and 15 nm or less in full width at half maximum.

As the image pickup means 50, one provided with an image pickup element having an image pickup field in an area including the measurement unit 30 in the microchannel chip 10 is used. Specifically, the image pickup field of the image pickup device of the image pickup unit 50 is a region where the measurement unit 30 is located and its peripheral region on the other surface of the microchannel chip 10 facing the image pickup device. In the illustrated example, a region including the measurement unit 30 and a part of the linear flow passage portions 20a and 20b in the first flow passage 20 and each of the plurality of second flow passages 25 is set as an imaging visual field of the image pickup device. The light from the light source 40 is radiated over the entire area of the imaging visual field.
As the image pickup means 50, for example, a CMOS camera equipped with a CMOS image pickup element is used. The imaging field of view of the CMOS image sensor of this CMOS camera, that is, the image size obtained by the CMOS camera is 640×480 pixels (corresponding to the region of the vertical and horizontal dimensions of the microchannel chip 10 of 1090×820 μm).
For example, an achromatic lens is used as the lens 51, and the magnification of the optical image by the lens 51 is, for example, 5 times.

The control mechanism 60 performs image processing on the image data of the image taken by the image pickup device of the image pickup means 50 to measure the luminance at the position (pixel position) of the measurement unit 30 in the image to determine the absorbance of the plasma component. It has a function to calculate. It also has a function of controlling a power supply 41 that supplies electricity to the light source 40.
In this example, the absorbance A _{455 at the} wavelength of 455 nm is calculated based on the blue luminance value of the image data obtained by image-processing the image captured by the image capturing means 50, and the green color of the image data is calculated. The absorbance A _{575 at} a wavelength of 575 nm is calculated based on the brightness value. Here, the absorbance A ₄₅₅ can be regarded as the sum of the absorbance of bilirubin and the absorbance of hemolyzed hemoglobin at a wavelength of 455 nm. On the other hand, the absorbance A ₅₇₅ can be regarded as the absorbance of hemolyzed hemoglobin at a wavelength of 575 nm. Then, the absorbance of hemolysis hemoglobin at a wavelength of 575nm, since a value approximating to the absorbance of hemolysis hemoglobin at a wavelength of 455nm, a value obtained by subtracting the absorbance A ₅₇₅ from the absorbance A ₄₅₅ a (A ₄₅₅ -A _575), at a wavelength of 455nm It can be regarded as the absorbance of bilirubin. The bilirubin concentration is calculated from the calibration curve obtained in advance and the value of A ₄₅₅ -A ₅₇₅ by utilizing the fact that the absorbance and the concentration have a proportional relationship (Lambert-Beer's law).

In such a sample concentration measuring apparatus, as described above, the specific component (this sample) separated from the liquid sample (blood in this example) is added to the measuring section 30 (wedge-shaped space 35) of the microchannel chip 10. In the example, blood plasma containing bilirubin, which is a component to be tested, is filled.
Then, in a state in which the specific component is filled in the measurement unit 30 of the micro-channel chip 10, the light emitted from the light source 40 passes through the optical filter 45 and the lens 48 and the measurement region 38 in the micro-channel chip 10. Is irradiated. The wavelength range of the light that passes through the optical filter 45, that is, the light that irradiates the measurement region 38 of the microchannel chip 10 is limited by the optical filter 45 to the wavelength region near 455 nm and the wavelength region near 575 nm. After that, an optical image of light that has passed through the measurement region 38 of the microchannel chip 10 is captured by the image capturing unit 50. Then, the concentration of bilirubin, which is the component to be inspected, is calculated based on the image data obtained by the imaging means 50.

According to the above-described sample concentration measuring device, the required amount of the specific component separated from the sample in the microchannel chip 10 is efficiently stored in the measurement region 38 of the measuring unit 30 by the capillary force of the wedge-shaped space 35 ( (Filling), it is possible to obtain high inspection efficiency. Further, since the measurement region 38 of the microchannel chip 10 to which the light from the light source 40 is irradiated has a constant thickness, the optical path length can be made constant and the concentration of a specific component is high. It can be measured with reliability.

The sample concentration measuring apparatus is not limited to the one having the above-described configuration, and as shown in FIG. 12, for example, a first light source 40a including an LED element that emits light having a peak emission wavelength of 450 nm and, for example, peak emission The second light source 40b including an LED element that emits light having a wavelength of 570 nm may be separately provided. In this sample concentration measuring apparatus, the first light source 40a is arranged so as to face the measurement unit 30 in the microchannel chip 10, and the second light source 40b is arranged with respect to the optical path of the light from the first light source 40a. It is arranged so that it faces the vertical direction. The first light source 40a and the second light source 40b are electrically connected to the power supply 41. At the intersection of the optical path of the light from the first light source 40a and the optical path of the light from the second light source 40b, the light from the first light source 40a is transmitted and the light from the second light source 40b is reflected. The dichroic mirror 42 is arranged in a state of being inclined at 45° with respect to each of the optical path of the light from the first light source 40a and the optical path of the light from the second light source 40b.

On the optical path between the first light source 40a and the dichroic mirror 42, a first optical filter 46a that limits the wavelength range of transmitted light is arranged. A lens 49a for collimating the incident light is arranged between the first optical filter 46a and the dichroic mirror 42. On the optical path between the second light source 40b and the dichroic mirror 42, a second optical filter 46b that limits the wavelength range of transmitted light is arranged. A lens 49b for collimating incident light is arranged between the second optical filter 46b and the dichroic mirror 42. Other configurations of the sample concentration measuring apparatus shown in FIG. 12 are similar to those of the sample concentration measuring apparatus shown in FIG.

In this sample concentration measuring apparatus, the operation of irradiating the measurement unit 30 of the microchannel chip 10 with light from the first light source 40a and the operation of irradiating light with the second light source 40b are performed simultaneously. However, after one of the operations is performed, the other operation may be performed.

[Production Example 1 of microchannel chip]
(1) Production of First Substrate and Second Substrate 50 parts by mass of polypropylene resin (“Novac (R) PP” manufactured by Nippon Polypro Co., Ltd.) and hydrogenated styrene/isoprene/butadiene block copolymer (Co., Ltd.) A specific resin composition was prepared by heating and kneading "HIBLER 7311" manufactured by Kuraray Co., Ltd., and 50 parts by mass of polystyrene block content=12% by mass). The melting point of the obtained specific resin composition was 142° C., the deflection temperature under load was 43° C., and the glass transition temperature was −35° C.
Then, by injection molding the prepared specific resin composition, the first substrate having the groove for the first flow path and the recess for the measurement portion formed on the surface, and the groove for the second flow path was formed on the surface. A second substrate was manufactured.
In the obtained first substrate, the first channel groove has a total length of 50 mm from the sample introducing part (21) to the first discharging part (23) (see FIG. 1) and a width (depth) in the thickness direction of the first substrate. Is 100 μm, and the width in the surface direction of the first substrate is 300 μm.
2 to 4, the measuring portion recess has a total length (length of a portion where a plurality of second flow paths are formed) of 15 mm, and a wedge-shaped space (35) has a length (L1) of 1 mm. The length (L2) of the measurement area is 0.5 mm. Further, the dimension (D) in the thickness direction of the first substrate in the portion forming the constant volume space (31) is 100 μm, the dimension (W1) in the surface direction of the first substrate at the opening end face is 200 μm, and the constant volume formation space is formed. The angle (γ1, γ2) formed by the pair of constant volume space forming surfaces (32a, 32b) with respect to the bottom surface of the measurement portion recess is 85°. In addition, the tip inclination angle (α) of the wedge-shaped space (35) is 45°, the opening angle (β) of the wedge-shaped space (35) is 11.4°, and the opening at one end position in the longitudinal direction of the measurement region The dimension (W2) of the end face in the surface direction of the first substrate is 20 μm.
In the obtained second substrate, the second flow path groove had a length of 0.5 mm, a width (depth) in the thickness direction of the second substrate of 2 μm, and a width (W3 in the plane direction of the second substrate. ) Is 50 μm, and the number of grooves for the second flow path is 300. The intervals between the adjacent second channel grooves are the same size (equal intervals).

(2) Hydrophilization treatment of the first substrate and the second substrate Using platinum sputtering, the inner walls of the first flow path groove and the measurement portion recess in the obtained first substrate, and the bonding to the second substrate A film was formed on the surface under predetermined conditions. Further, the groove for the first flow path and the recess for the measurement section were made hydrophilic by immersing in an aqueous thiol sulfonate solution and air-drying. The contact angle of water on the surface subjected to the hydrophilic treatment was 14°.
Further, using platinum sputtering, a film was formed on the inner wall surface of the second flow path groove in the obtained second substrate under predetermined conditions. Furthermore, the groove for the first flow path and the recess for the measurement portion were hydrophilized by immersing in a sulfonic acid thiol solution aqueous solution and air-drying. The contact angle of water on the surface subjected to the hydrophilic treatment was 86°.

(3) Manufacture of Micro Channel Chip The first substrate was aligned and brought into contact with the bonding surface of the second substrate. Then, the first substrate and the second substrate are heated at 60° C. to bond the first substrate and the second substrate by utilizing the self-bonding property, and thus, the micro channel chip (hereinafter, referred to as “micro Flow channel chip A”) was manufactured.
In the obtained microchannel chip, the length from the upstream end of the first channel to the branch point with the second channel branched on the most upstream side of the first channel is 5 mm.
When the second channel of the obtained microchannel chip was observed with a microscope, no abnormality such as deformation was observed.

[Production Examples 2 to 4 of Micro Channel Chip]
A microchannel chip (hereinafter referred to as "microchannel chip B") was prepared in the same manner as in Microchannel chip manufacturing example 1 except that the film forming conditions for platinum sputtering were changed as appropriate for the hydrophilic treatment of the second substrate. -"Microchannel chip D") was manufactured. The contact angle of water on the inner wall surface of the second channel in the micro channel chip B is 51°, the contact angle of water on the inner wall surface of the second channel in the micro channel chip C is 24°, and the micro channel chip The contact angle of water on the inner wall surface of the second flow path in D is 14°.

[Comparative Production Example 1 of Micro Channel Chip]
In addition to forming a measuring part recess having a substantially constant space shape in the length direction (a measuring part recess that does not have a wedge-shaped space but only a constant volume space), A comparative first substrate having the same structure as that manufactured in Manufacturing Example 1 was manufactured. The measuring portion recess in the first substrate for comparison has a total length (the length of the portion where the plurality of second flow paths are formed) of 20 mm, the thickness direction dimension of the first substrate is 100 μm, and The dimension of one substrate in the surface direction is 200 μm, and the angle formed by the pair of measurement portion formation surfaces with respect to the bottom surface of the measurement portion recess is 85°.
A microchannel chip for comparison was produced in the same manner as in Production Example 1 of microchannel chip except that this first substrate for comparison was used.

<Example 1>
For each of the above-described microchannel chips A to D, human blood was introduced and allowed to stand for 10 minutes, and then the absorbance of hemolyzed hemoglobin (hemolytic intensity) in the liquid filled in the measurement part of the microchannel chip was measured. .. Results are shown in FIG. It was confirmed that hemolysis did not occur in the microchannel chip A. Further, it was confirmed that the degree of hemolysis increases as the contact angle of water on the inner wall surface of the second flow channel decreases, and if the contact angle of water is 70° or more and less than 90°, there is a practical problem. It was confirmed that hemolysis can be prevented to the extent that it does not occur.

<Example 2>
Water was introduced as a test fluid into each of the microchannel chip A and the microchannel chip for comparison, and the filling amount (storage length) of the test fluid in the measuring portion with respect to the elapsed time was examined. The results are shown in Fig. 14. In FIG. 14, a curve a (square plot) is the result for the microchannel chip A, and a curve b (circle plot) is the result for the microchannel chip for comparison. Here, in the microchannel chip A, the storage length of the test fluid in the measurement section refers to the length in the extending direction of the measurement section from the boundary position between the wedge-shaped space and the constant volume space.
From the above results, it was confirmed that, according to the microchannel chip A of the present invention, the component to be inspected can be filled in the measurement portion in a short time.

10 Micro Channel Chip 11 Chip Base 12 First Substrate 13a First Channel Groove 13b Measuring Section Recess 15 Second Substrate 16 Second Channel Groove 20 First Channel 20a Linear Channel Section 20b Linear Channel Part 20c Bottom wall surface 21 Specimen introduction part 22 Specimen storage part 23 First discharge part 25 Second flow path 27 Third flow path 28 Second discharge part 30 Measuring part 30a Upper bottom surface 30b Lower bottom surface 31 Constant volume space 32a Constant volume space formation Surface 32b Constant volume space forming surface 35 Wedge space 36a Wedge space forming surface 36b Wedge space forming surface 38 Measurement area 40 Light source 40a First light source 40b Second light source 41 Power supply 42 Dichroic mirror 45 Optical filter 46a First Optical filter 46b Second optical filter 48 Lens 49a Lens 49b Lens 50 Imaging means 51 Lens 60 Control mechanism BC Blood cell component C Ridge line PL Plasma component (specific component)

Claims (5)

A first channel for circulating a liquid sample, a plurality of second channels for separating a specific component from the sample flowing through the first channel, and a specific component separated from the sample are filled. It consists of a plate-shaped body with a measuring part inside,
Each of the plurality of second flow paths is a component to be excluded from the sample, which is opened in the flow path forming surface forming the first flow path and communicates with the first flow path and is connected to the measurement unit. Do a groove having a width of dimension capable of blocking the entry for the second channel Ri,
The measurement unit has a wedge-shaped space in which the gap gradually decreases in one direction of the surface direction, and a constant volume space having substantially the same spatial shape in the one direction continuous with the wedge-shaped space. Cage,
An angle formed by two continuous constant volume space forming surfaces that are represented in a cross section perpendicular to the one direction of the constant volume space is γ, and a pair of mutually facing sides that are represented in a side view from the surface direction of the wedge-shaped space. The micro flow channel chip is characterized in that the wedge-shaped space has a space shape that satisfies a relationship of α<γ, where α is an angle formed by the wedge-shaped space forming surface. When the angle formed by a pair of wedge-shaped space forming surfaces facing each other, which is represented by a plan view from the thickness direction of the wedge-shaped space, is β, the wedge-shaped space has a space shape satisfying a relationship of β<γ. The microchannel chip according to claim 1, which further comprises: The micro channel according to claim 1 or 2, wherein the first channel has a width of 10 µm or more and 1000 µm or less, and the second channel has a width of 0.1 µm or more and 1.2 µm or less. Chips. The measurement unit has a measurement region having a constant dimension in the thickness direction, and the dimension in the thickness direction of the measurement region is 10 to 1000 μm. 3. The microchannel chip according to any one of 3 above. 5. The hydrophilicity of the flow path forming surface forming the second flow path is lower than the hydrophilicity of the flow path forming surface forming the first flow path. micro-channel chip.

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