WO2020013256A1 - Flow path, method for producing flow path, electrode structure, and method for producing electrode structure - Google Patents

Flow path, method for producing flow path, electrode structure, and method for producing electrode structure Download PDF

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Publication number
WO2020013256A1
WO2020013256A1 PCT/JP2019/027436 JP2019027436W WO2020013256A1 WO 2020013256 A1 WO2020013256 A1 WO 2020013256A1 JP 2019027436 W JP2019027436 W JP 2019027436W WO 2020013256 A1 WO2020013256 A1 WO 2020013256A1
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hole
atomic layer
less
coating layer
layer
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PCT/JP2019/027436
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French (fr)
Japanese (ja)
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真楠 筒井
正輝 谷口
川合　知二
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国立大学法人大阪大学
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Publication of WO2020013256A1 publication Critical patent/WO2020013256A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means

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  • the present invention relates to a flow path, a method for manufacturing a flow path, an electrode structure, and a method for manufacturing an electrode structure.
  • the charge on the wall surface of the channel for moving the sample has a great effect on the movement and / or detection of the sample (for example, see Patent Document 1). .
  • the wall surface of a flow channel is coated with a desired material by a chemical vapor deposition method, molecular modification, or the like, thereby adjusting the charge on the wall surface of the flow channel.
  • the charge on the wall of the flow channel can only be roughly controlled by the isoelectric point of the material used for coating, and the charge on the wall of the flow channel cannot be precisely controlled.
  • One object of one embodiment of the present invention is to provide a technique for precisely controlling the charge on the wall surface of a flow channel.
  • a channel according to one embodiment of the present invention is provided with a base material provided with a through-hole that is a path through which a substance moves, and provided on a wall surface of the through-hole. And a coating layer including an atomic layer.
  • an electrode structure includes a flow channel according to one embodiment of the present invention, and an electrode pair arranged to sandwich the through hole. It is characterized by having.
  • a method for manufacturing a flow channel includes an atomic layer on a wall surface of a through-hole provided in a base material, which is a path through which a substance moves.
  • a coating layer forming step of forming a coating layer is a step of forming a coating layer.
  • a method for manufacturing an electrode structure according to one embodiment of the present invention includes an atomic layer provided on a base material, on a wall surface of a through hole that is a path through which a substance moves. And forming an electrode pair so as to sandwich the through hole.
  • the charge on the wall surface of the flow path can be precisely controlled.
  • FIGS. 301 and 302 are schematic diagrams of the apparatus used in the embodiment of the present invention.
  • Reference numerals 401 to 404 show test results in the example of the present invention.
  • 501 to 505 are diagrams showing test results in the examples of the present invention.
  • 601 and 602 are diagrams showing test results in the example of the present invention.
  • FIG. 1 shows an electrode structure according to an embodiment of the present invention.
  • the electrode structure can be used as a substance transfer device, a substance detection device, a substance identification device, or the like.
  • the electrode structure includes a flow path 1 and an electrode pair including a negative electrode 2 and a positive electrode 3.
  • the through hole provided in the flow path 1 is filled with a solvent (for example, water), and the substance to be detected moves in the solvent.
  • an ionic current flows between the electrode pairs via the through holes.
  • the substance moves in the through hole by the electric field.
  • the magnitude of the ionic current flowing between the negative electrode 2 and the positive electrode 3 differs between when the substance is present in the through hole and when no substance is present in the through hole. More specifically, when a substance is present in the through hole, the substance blocks the ionic current, and the ionic current flowing between the negative electrode 2 and the positive electrode 3 decreases. Therefore, a substance passing through the through-hole can be detected or identified by detecting a change in the ionic current with the ammeter 4.
  • FIG. 2 shows the detailed structure of the wall surface of the flow channel 1 in a region surrounded by a broken line in FIG. 2 is a diagram showing a wall surface of the flow channel 1 according to an embodiment of the present invention
  • 202 of FIG. 2 is a diagram showing a wall surface of a conventional flow channel.
  • the solvent contacts the surface of the base material 10, and the surface of the base material 10 on the side in contact with the solvent. Generates electric charge.
  • the base material 10 is covered with the coating layer 20 including the atomic layer.
  • the atomic layer is a very thin layer so that the solvent can easily penetrate into the atomic layer.
  • the solvent that has penetrated into the atomic layer comes into contact with the surface of the substrate 10, and a charge is generated on the surface of the substrate 10 on the side in contact with the solvent, as in the case where the substrate 10 is not covered with the coating layer 20.
  • the flow channel 1 (in other words, the through-hole) is formed by two kinds of charges, the surface charge of the coating layer 20 and the surface charge of the substrate 10.
  • the surface charge of the wall surface can be precisely controlled.
  • the surface charge of the flow path 1 can be precisely controlled, for example, (i) weakening the Coulomb interaction between the substance and the wall surface of the flow path 1 and / or (ii) It becomes possible to weaken the electroosmotic flow which flows near the wall surface and hinders the movement of the substance. If these controls become possible, it becomes easier for the substance to pass through the through-hole. If the substance easily passes through the through-hole, it is possible to analyze (for example, detect or identify a substance in the sample) without concentrating the sample even a sample containing a trace amount of the substance. .
  • reference numeral 202 in FIG. 2 shows a conventional flow path including the base material 10 and the coating layer 20.
  • the base material 10 is covered with the coating layer 20 containing no atomic layer.
  • Such a coating layer 20 is a very thick layer because it is formed by a chemical vapor deposition method, molecular modification, or the like. The solvent cannot penetrate into such a very thick coating layer 20. Therefore, no charge is generated on the surface of the base material 10 in the conventional flow path.
  • the surface charge of the flow path (in other words, the wall surface of the through hole) is controlled only by the surface charge of the coating layer 20, so that the flow path (in other words, the wall surface of the through hole) is controlled.
  • the surface charge cannot be precisely controlled.
  • the flow channel of the present embodiment includes a base material provided with a through hole that is a path through which a substance moves, and a coating layer including an atomic layer, which is provided on a wall surface of the through hole. It has something.
  • atomic layer refers to a layer in which specific atoms are formed in a plane, and the layer has a thickness of one specific atom. Intended.
  • the substance may be, for example, a substance to be detected or identified.
  • the substance include an atom, a molecule, a polymer, and a complex thereof. More specifically, examples of the substance include nucleic acids (DNA or RNA), amino acids, proteins, pollen, viruses, fungi, cells, organic particles, and inorganic particles.
  • a desired solvent or a gel containing a solvent can be filled in the through-hole.
  • the solvent include an aqueous solution containing water, TE buffer (Tris-HCl, EDTA buffer), and chloride (eg, KCl, LiCl, or NaCl).
  • the gel include polyacrylamide gel, agarose gel, dextran, and polyethylene glycol.
  • the solvent may include an electrolyte. Examples of the electrolyte include KCl, NaCl, and LiCl.
  • the flow path includes a base material provided with a through-hole, which is a path through which a substance moves.
  • the shape of the base material itself is not particularly limited, and may be a plate shape or a column shape.
  • the material of the base material is not particularly limited, and examples thereof include silicon nitride, silicon dioxide, metal, zinc oxide, titanium dioxide, hafnium oxide, and alumina. Among these materials, alumina is preferred because of the advantageous effect of obtaining good biocompatibility.
  • the shape of the through-hole is not particularly limited, and may be, for example, a cylinder or a polygonal pillar. If the shape of the through-hole is a cylinder, or a polygonal pillar, the diameter of the circle at the bottom of the cylinder, and the diameter of the circumscribed circle at the bottom of the polygonal pillar are not particularly limited, and may vary depending on the size of the moving substance. Accordingly, it can be set appropriately.
  • the diameter A of the circle and the diameter A of the circumscribed circle are, for example, 0.1 nm to 100 ⁇ m, 0.1 nm to 10 ⁇ m, 0.1 nm to 1 ⁇ m, 0.1 nm to 100 nm, 0.1 nm to 10 nm, or 1 nm to 100 nm. It may be 10 nm.
  • the depth B of the through hole is not particularly limited, and is, for example, 0.1 nm to 100 ⁇ m, 0.1 nm to 10 ⁇ m, 0.1 nm to 1 ⁇ m, 0.1 nm to 100 nm, 0.1 nm to 10 nm, or 1 nm to 10 nm. It may be.
  • the aspect ratio (depth B / diameter A) of the through-hole is not particularly limited, and is, for example, 1/1000 to 1/1, 1/100 to 1/1, or 1/10 to 1/1. Is also good. Since the advantageous effect that the spatial resolution of the nanopore sensor is improved is obtained, the smaller the aspect ratio of the through hole, the more preferable.
  • the difference increases. Therefore, when the channel according to the present embodiment is used for a substance detection device or a substance identification device, the detection sensitivity of the substance or the identification accuracy of the substance can be improved.
  • a coating layer including an atomic layer is provided on the wall surface of the through hole. Note that the coating layer may be provided not only on the wall surface of the through hole but also on the entire base material.
  • the coating layer may include an atomic layer or a stack of atomic layers, or may be an atomic layer or a stack of atomic layers.
  • the atomic layer has (i) a charge of “ ⁇ ” when the substance that electrophoreses in the through hole has a “ ⁇ ” charge, and a charge of “+” when the substance electrophoreses in the through hole.
  • the atomic layer has an electric charge of “+” and (ii) the atomic layer has a small value of ⁇ potential.
  • the value of the ⁇ potential is preferably as small as possible. With such a configuration, the substance is easily electrophoresed in the through hole.
  • the value of the ⁇ potential can be adjusted by adjusting the thickness of the atomic layer (for example, see FIG. 4 of an embodiment described later). From the viewpoint of more accurately adjusting the thickness of the atomic layer, it is preferable to form the atomic layer by an atomic layer deposition method (Atomic Layer Deposition: ALD).
  • the material constituting the atomic layer is not particularly limited, and examples thereof include Al 2 O 3 , HfO 2 , TiO 2 , ZnO, and SiO 2 .
  • the thickness of the atomic layer can be easily adjusted to a desired thickness.
  • Al 2 O 3 is preferable because it has an advantageous effect of obtaining good biocompatibility.
  • the thickness of the coating layer is preferably 200 times or less the thickness of the atomic layer, but is 190 times or less, 180 times or less, 170 times or less, 160 times or less, 150 times or less, 140 times or less, 130 times or less. 120 times or less, 110 times or less, 100 times or less, 90 times or less, 80 times or less, 70 times or less, 60 times or less, 50 times or less, 40 times or less, 30 times or less, 20 times or less, or 10 times or less It may be.
  • the lower limit of the thickness of the coating layer is not particularly limited, but may be 1, 2, 3, 4, or 5 times the thickness of the atomic layer.
  • the coating layer may include a stacked body of atomic layers, or may be formed of a stacked body of atomic layers.
  • the coating layer is, for example, (i) 200 or less, 190 or less, 180 or less, 170 or less, 160 or less, 150 or less, 140 or less, 130 or less, 120 or less, 110 or less, 100 or less It has at most 90, up to 90, at most 80, at most 70, at most 60, at most 50, at most 40, at most 30, at most 20, at most 20, and at most 10 atomic layers.
  • it may be composed of 90 or less, 80 or less, 70 or less, 60 or less, 50 or less, 40 or less, 30 or less, 20 or less, or 10 or less atomic layers.
  • the lower limit of the number of atomic layers constituting the coating layer is not particularly limited, and may be, for example, one layer, two layers, three layers, four layers, or five layers.
  • the thickness of the atomic layer is determined according to the material constituting the atomic layer, and the thickness is well known (see, for example, literature Rev. ⁇ Sci. ⁇ Instrum. ⁇ 73, ⁇ 2981-2987 ⁇ (2002)). This reference is incorporated herein by reference.
  • the method for manufacturing a channel according to the present embodiment includes a coating layer forming step of forming a coating layer including an atomic layer on a wall surface of a through-hole that is provided on a base material and that is a path through which a substance moves. Have.
  • atomic layer deposition As a method of forming an atomic layer included in the film layer, a known atomic layer deposition method (Atomic Layer Deposition: ALD) can be mentioned. If an atomic layer is formed by an atomic deposition method, a desired number of atomic layers can be accurately formed.
  • ALD atomic Layer Deposition
  • the electrode structure according to the present embodiment includes (i) a base material provided with a through-hole as a path through which a substance moves, and a coating including an atomic layer provided on a wall surface of the through-hole. And (ii) an electrode pair disposed so as to sandwich the through hole.
  • the electrode pair is not particularly limited, and a well-known electrode pair (for example, a silver / silver chloride (Ag / AgCl) electrode) may be appropriately used.
  • the thickness of the coating layer is preferably 200 times or less the thickness of the atomic layer, but is 190 times or less, 180 times or less, 170 times or less, 160 times or less, 150 times or less, 140 times or less, 130 times or less. 120 times or less, 110 times or less, 100 times or less, 90 times or less, 80 times or less, 70 times or less, 60 times or less, 50 times or less, 40 times or less, 30 times or less, 20 times or less, or 10 times or less It may be.
  • the lower limit of the thickness of the coating is not particularly limited, but may be 1, 2, 3, 4, or 5 times the thickness of the atomic layer.
  • the coating layer may include a stacked body of atomic layers, or may be formed of a stacked body of atomic layers. Since the number of the atomic layers constituting the coating layer has already been described, the description thereof is omitted here.
  • the method for manufacturing an electrode structure according to the present embodiment includes a coating layer forming step of forming a coating layer including an atomic layer on a wall surface of a through hole provided in a base material, which is a path through which a substance moves. And an electrode pair forming step of providing an electrode pair so as to sandwich the through hole.
  • atomic layer deposition As a method of forming an atomic layer included in the film layer, a known atomic layer deposition method (Atomic Layer Deposition: ALD) can be mentioned. If an atomic layer is formed by an atomic deposition method, a desired number of atomic layers can be accurately formed.
  • ALD atomic Layer Deposition
  • a specific method of providing the electrode pair is not limited, and the electrode pair may be provided so as to sandwich the through hole.
  • the coating layer is formed so as to have a thickness of 200 times or less the thickness of the atomic layer.
  • the thickness of the coating layer is 190 times or less, 180 times or less, 170 times or less, 160 times or less, 150 times or less, 140 times or less, 130 times or less, 120 times or less, 110 times or less, 100 times or less, 90 times or less. , 80 times or less, 70 times or less, 60 times or less, 50 times or less, 40 times or less, 30 times or less, 20 times or less, or 10 times or less.
  • the lower limit of the thickness of the coating layer is not particularly limited, but may be 1, 2, 3, 4, or 5 times the thickness of the atomic layer.
  • the solvent can easily come into contact with the surface of the substrate, and as a result, a desired charge can be stably generated on the surface of the substrate.
  • the coating layer may include a stacked body of atomic layers, or may be formed of a stacked body of atomic layers. Since the number of the atomic layers constituting the coating layer has already been described, the description thereof is omitted here.
  • the flow channel according to one embodiment of the present invention is provided with a base material provided with a through hole that is a path through which a substance moves, and a coating layer including an atomic layer, which is provided on a wall surface of the through hole. , Are provided.
  • the coating layer including the atomic layer has a charge on its surface. Further, the atomic layer is a very thin layer, and a solvent (eg, water) filled in the flow path can easily enter the atomic layer. The solvent that has penetrated into the atomic layer comes into contact with the surface of the substrate, and charges are generated on the surface of the substrate. Therefore, with the above configuration, the surface charge on the wall surface of the through-hole can be precisely controlled by two kinds of charges, the surface charge of the coating layer including the atomic layer and the surface charge of the base material. .
  • a solvent eg, water
  • the thickness of the coating layer is preferably 200 times or less the thickness of the atomic layer.
  • the atomic layer is preferably an atomic layer of Al 2 O 3 , HfO 2 , TiO 2 , ZnO, or SiO 2 .
  • the thickness of the atomic layer can be easily adjusted to a desired thickness.
  • An electrode structure according to one embodiment of the present invention includes the channel according to one embodiment of the present invention, and an electrode pair arranged so as to sandwich the through hole.
  • an electric field is formed by the electrode pairs, an ionic current flows between the electrode pairs via the through holes.
  • the substance moves in the through hole by the electric field.
  • the magnitude of the ionic current differs between when a substance is present in the through hole and when no substance is present in the through hole. Therefore, a substance can be detected by detecting a change in the ion current. Since the surface charge on the wall surface of the through hole is precisely controlled, the substance can easily move through the through hole, and as a result, the substance can be detected with high accuracy.
  • the method for manufacturing a flow channel includes forming a coating layer including an atomic layer on a wall surface of a through-hole provided in a base material, which is a path through which a substance moves. It is characterized by having a process.
  • the coating layer including the atomic layer has a charge on its surface. Further, the atomic layer is a very thin layer, and a solvent (eg, water) filled in the flow path can easily enter the atomic layer. The solvent that has penetrated into the atomic layer comes into contact with the surface of the substrate, and charges are generated on the surface of the substrate. Therefore, with the above configuration, the surface charge on the wall surface of the through-hole can be precisely controlled by two kinds of charges, the surface charge of the coating layer including the atomic layer and the surface charge of the base material. .
  • a solvent eg, water
  • the coating layer is formed so as to have a thickness of 200 times or less the thickness of the atomic layer.
  • the atomic layer is preferably an atomic layer of Al 2 O 3 , HfO 2 , TiO 2 , ZnO, or SiO 2 .
  • the thickness of the atomic layer can be easily adjusted to a desired thickness.
  • the atomic layer is formed by an atomic layer deposition method.
  • the thickness of the atomic layer can be easily and accurately adjusted to a desired thickness.
  • a method for manufacturing an electrode structure comprising: forming a coating layer containing an atomic layer on a wall surface of a through-hole provided in a substrate, which is a path through which a substance moves.
  • the method is characterized by including a forming step and an electrode pair forming step of providing an electrode pair so as to sandwich the through hole.
  • an electric field is formed by the electrode pairs, an ionic current flows between the electrode pairs via the through holes.
  • the substance moves in the through hole by the electric field.
  • the magnitude of the ionic current differs between when a substance is present in the through hole and when no substance is present in the through hole. Therefore, a substance can be detected by detecting a change in the ion current. Since the surface charge on the wall surface of the through hole is precisely controlled, the substance can easily move through the through hole, and as a result, the substance can be detected with high accuracy.
  • the coating layer is formed to have a thickness of 200 times or less the thickness of the atomic layer.
  • the atomic layer is preferably an atomic layer of Al 2 O 3 , HfO 2 , TiO 2 , ZnO, or SiO 2 .
  • the thickness of the atomic layer can be easily adjusted to a desired thickness.
  • the atomic layer is formed by an atomic layer deposition method.
  • the thickness of the atomic layer can be easily and accurately adjusted to a desired thickness.
  • the exposed Si wafer was deeply etched in a KOH aqueous solution at 120 ° C. to form a 50 nm thick Si 3 N 4 film.
  • An electron beam resist layer (ZEP-520A-7) was formed on the Si 3 N 4 film by spin coating, and a circle having a diameter of 1.2 ⁇ m was drawn by electron beam lithography.
  • the Si 3 N 4 film was shaved by dry etching, thereby forming a through hole having a diameter of 1.2 ⁇ m and a depth of 50 nm.
  • the Si wafer in which the through hole was formed was immersed in N, N-dimethylformamide all day and night, thereby removing shavings.
  • the Si wafer was cleaned using ethanol and acetone.
  • trimethylaluminum and water precursors water Precursors
  • the Si wafer uniformly covered with the Al 2 O 3 layer.
  • the thickness of the atomic layer constituting the Al 2 O 3 layer was precisely controlled to 0.12 nm by controlling the number of reaction cycles.
  • the thickness of the Al 2 O 3 layer is 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, or 6 nm
  • the thickness of each of these Al 2 O 3 layers is eight times the thickness of the atomic layer. , 17 times, 25 times, 33 times, 42 times, or 50 times.
  • the Si wafer having the through-hole formed therein was sealed with two polymer blocks formed of polydimethylsiloxane. Specifically, first, the surface of each of the Si wafer on which the through hole was formed and the polymer block was activated by oxygen plasma. Next, a composite block bonded to each other was produced by combining the Si wafer with the through-hole formed therein and the polymer block.
  • the space on one side sandwiching the through-hole was filled with particles (carboxylated polystyrene particles (0.78 ⁇ m in diameter, Thermo Scientific)) at a concentration of 0.3 pM.
  • the space on the other side sandwiching the through hole was filled with 0.1 ⁇ PBS in which the particles were not dispersed.
  • the ion current was measured by applying a dc voltage Vb of 0.1 V and recording the output power at a sampling rate of 1 MHz.
  • Vb dc voltage
  • Vb dc voltage
  • a digitizer National Instruments
  • ⁇ ⁇ ⁇ ⁇ Bias polarity was set in order to electrophoretically pull negatively charged polystyrene particles into the through-holes.
  • Al 2 O 3 layer having a thickness of t ALD was inserted at the boundary between the electrolyte and the substrate.
  • the surface potential distribution at the boundary of Al 2 O 3 and Si 3 N 4 was calculated under the variable charge density ⁇ Al2O3 / Si3N4. 9.0 and 9.7 were used as the dielectric constants of Al 2 O 3 and Si 3 N 4 .
  • the mobility of Na + and Ci ⁇ in 0.1 ⁇ PBS buffer (solution containing 13.7 mM NaCl) was 5.19 ⁇ 10 ⁇ 8 m 2 V ⁇ 1 S ⁇ 1 and 7.91 ⁇ 10 -8 m 2 V ⁇ 1 S ⁇ 1 was used.
  • Simulation of ion transport was performed using COMSOL equipped with an AC / DC module, a reaction engineering module, and a Computational Fluid Dynamics (CFD) module.
  • the surface charge density of the polystyrene particles and the surface charge density of the wall surface of the through-hole were calculated according to the zeta potential measured using a Zetasizer (Malvern @ Panalytical).
  • the properties of the bulk were those of water, Si 3 N 4 , and Al 2 O 3 .
  • Test result 1> The thickness t m was formed on the Si 3 N 4 film in a 50 nm, the diameter d pore is a through-hole is 1.2 [mu] m, was covered by the Al 2 O 3 layer with varying thickness T ALD The ion current I ion flowing through the through-hole was measured using 0.1 ⁇ PBS (Merck Millipore) with the dc voltage Vb within the range of ⁇ 0.5 V. The result is shown at 401 in FIG.
  • the conductance G open of the through hole was 180 ⁇ 14 nS. Holes covered by the Al 2 O 3 layer showed similar conductance G open a through hole that is not covered by the Al 2 O 3 layer. Since the thickness T ALD of the Al 2 O 3 layer is smaller than the diameter d pore and the thickness t m , it is considered that the same conductance G open was exhibited.
  • the measurement results of a zeta potential zeta s shown in 402 of FIG. As shown in 402 of FIG. 4, while the T ALD decreases from 0 to 1, the value of the zeta s decreases sharply, while the T ALD increases from 1 to 6, the value of the zeta s increased. Also, if T ALD is greater than 6, the value of zeta s was nearly constant.
  • FIG. 403 of FIG. 4 shows a state near the wall surface of the through-hole, which is suggested from the above-described embodiment.
  • ⁇ Si3N4 -25mC / m 2
  • ⁇ Al2O3 -15mC / it can be modeled as a layer having a negative surface charge of m 2. From 404 in FIG.
  • the Al 2 O 3 atomic layer allows water molecules to permeate, and as a result, a surface charge is generated on the Si 3 N 4 surface even after the atomic layer is formed, and (Ii) Since the transmission distance of water molecules is finite, it has been found that the charge density at the Si 3 N 4 / Al 2 O 3 interface, and consequently the effective surface potential, can be controlled by the thickness of the atomic layer.
  • Test result 2> In this example, particles passing through the through-hole were detected.
  • Reference numeral 501 in FIG. 5 shows the I ion when T ALD is 4 nm.
  • T ALD was thicker than 10 nm, the particles could not pass through the through-hole and were trapped inside the through-hole. This is believed to act between the particles and the positively charged the Al 2 O 3 layer surface, is caused strong Coulomb attractive force is.
  • each particle is estimated from the ion spike width t d that indicates the time taken to pass through the through hole.
  • Reference numeral 503 in FIG. 5 shows a correlation between t d and t ALD .
  • An electroosmotic flow flowing in the through hole is shown at 504 in FIG.
  • the value of zeta s depending on the value of T ALD changes.
  • the speed of the electroosmotic flow changes in proportion to the absolute value of the value of T ALD .
  • the speed of the particles is determined by the electrophoretic force acting on the particles and the electroosmotic force acting on the particles. Therefore, as the speed of the electroosmotic flow changes, so does the speed of the particles.
  • reference numeral 505 shows the particle velocity measured in this test and the theoretical particle velocity in consideration of the electroosmotic flow. From 505 in FIG. 5, it was found that the particle velocity measured in the present test and the theoretical particle velocity in consideration of the electroosmotic flow coincide.
  • V EP speed of electrophoresis
  • V EOF speed of electroosmotic flow
  • the present invention can be widely used for technology using a fine channel.
  • the present invention can be used, for example, in the fields of detecting a substance, identifying a substance, and moving a substance.

Abstract

A flow path (1) comprising: a substrate in which there is provided a through-hole, which is a channel through which a substance moves; and a coating layer provided on a wall surface of the through-hole, the coating layer including an atomic layer. Through using the flow path (1), the charge of the wall surface of the flow path (1) is precisely controlled.

Description

流路、流路の製造方法、電極構造体、および、電極構造体の製造方法Channel, method of manufacturing channel, electrode structure, and method of manufacturing electrode structure
　本発明は、流路、流路の製造方法、電極構造体、および、電極構造体の製造方法に関する。 The present invention relates to a flow path, a method for manufacturing a flow path, an electrode structure, and a method for manufacturing an electrode structure.
　マイクロ流路センサデバイス、および、ナノ流路センサデバイスでは、検体を移動させる流路の壁面の電荷が、検体の移動および／または検出に対して大きな影響を及ぼす（例えば、特許文献１を参照）。 In the micro-channel sensor device and the nano-channel sensor device, the charge on the wall surface of the channel for moving the sample has a great effect on the movement and / or detection of the sample (for example, see Patent Document 1). .
　例えば、流路の壁面の電荷が大きいと、検体と流路の壁面との間のクーロン相互作用が大きくなる。その結果、検体が流路の壁面に吸着し、流路が詰まるという問題が発生する。 For example, if the charge on the wall of the channel is large, the Coulomb interaction between the specimen and the wall of the channel will increase. As a result, there arises a problem that the sample is adsorbed on the wall surface of the flow path and the flow path is clogged.
　また、流路の壁面の電荷が大きいと、流路の壁面の近傍に、多量の陰イオンまたは陽イオンが引き寄せられる。電界によって検体を移動させようとすると、当該電界が、多量の陰イオンまたは陽イオンをも移動させる。多量の陰イオンまたは陽イオンが移動すると大きな電気浸透流が発生し、電気浸透流の方向と検体の移動方向とが異なる場合には、電気浸透流が検体の移動を妨げるという問題が発生する。 と If the charge on the wall of the flow channel is large, a large amount of anions or cations are attracted near the wall of the flow channel. If the analyte is moved by an electric field, the electric field also moves a large amount of anions or cations. When a large amount of anions or cations move, a large electroosmotic flow is generated. When the direction of the electroosmotic flow is different from the moving direction of the sample, a problem occurs in that the electroosmotic flow hinders the movement of the sample.
　上述した問題を避けるためには、検体を移動させる流路の壁面の電荷を適切に調節する必要がある。従来から、化学気層蒸着法、または、分子修飾などによって、流路の壁面を所望の材料を用いてコーティングし、これによって、流路の壁面の電荷を調節している。 電荷 In order to avoid the above-mentioned problems, it is necessary to appropriately adjust the charge on the wall surface of the channel for moving the sample. 2. Description of the Related Art Conventionally, the wall surface of a flow channel is coated with a desired material by a chemical vapor deposition method, molecular modification, or the like, thereby adjusting the charge on the wall surface of the flow channel.
日本国公開特許公報「特開２０１６－１９７０７７号公報」Japanese Unexamined Patent Publication "JP-A-2016-19777"
　しかしながら、上述のような従来技術は、流路の壁面の電荷を、コーティングに用いる材料の等電点によって粗く制御することしかできず、流路の壁面の電荷を精密に制御することができない。 However, in the above-described conventional technology, the charge on the wall of the flow channel can only be roughly controlled by the isoelectric point of the material used for coating, and the charge on the wall of the flow channel cannot be precisely controlled.
　本発明の一態様は、流路の壁面の電荷を精密に制御する技術を提供することを目的とする。 One object of one embodiment of the present invention is to provide a technique for precisely controlling the charge on the wall surface of a flow channel.
　上記の課題を解決するために、本発明の一態様に係る流路は、物質が移動する経路である貫通孔が設けられている基材と、上記貫通孔の壁面上に設けられている、原子層を含んでいる被膜層と、を備えていることを特徴とする。 In order to solve the above problems, a channel according to one embodiment of the present invention is provided with a base material provided with a through-hole that is a path through which a substance moves, and provided on a wall surface of the through-hole. And a coating layer including an atomic layer.
　上記の課題を解決するために、本発明の一態様に係る電極構造体は、本発明の一態様に係る流路と、上記貫通孔を挟むように配置されている電極対と、を備えていることを特徴とする。 In order to solve the above problem, an electrode structure according to one embodiment of the present invention includes a flow channel according to one embodiment of the present invention, and an electrode pair arranged to sandwich the through hole. It is characterized by having.
　上記の課題を解決するために、本発明の一態様に係る流路の製造方法は、基材に設けられている、物質が移動する経路である貫通孔の壁面上に、原子層を含んでいる被膜層を形成する被膜層形成工程を有していることを特徴とする。 In order to solve the above problems, a method for manufacturing a flow channel according to one embodiment of the present invention includes an atomic layer on a wall surface of a through-hole provided in a base material, which is a path through which a substance moves. A coating layer forming step of forming a coating layer.
　上記の課題を解決するために、本発明の一態様に係る電極構造体の製造方法は、基材に設けられている、物質が移動する経路である貫通孔の壁面上に、原子層を含んでいる被膜層を形成する被膜層形成工程と、上記貫通孔を挟むように電極対を設ける電極対形成工程と、を有することを特徴とする。 In order to solve the above problem, a method for manufacturing an electrode structure according to one embodiment of the present invention includes an atomic layer provided on a base material, on a wall surface of a through hole that is a path through which a substance moves. And forming an electrode pair so as to sandwich the through hole.
　本発明の一態様によれば、流路の壁面の電荷を精密に制御することができる。 According to one embodiment of the present invention, the charge on the wall surface of the flow path can be precisely controlled.
本発明の一実施形態に係る電極構造体を示す図である。It is a figure showing the electrode structure concerning one embodiment of the present invention. ２０１は、本発明の一実施形態に係る流路の壁面を示す図であり、２０２は、従来技術の流路の壁面を示す図である。201 is a diagram showing a wall surface of a flow channel according to an embodiment of the present invention, and 202 is a diagram showing a wall surface of a conventional flow channel. ３０１および３０２は、本発明の実施例にて用いた装置の概略を示す図である。FIGS. 301 and 302 are schematic diagrams of the apparatus used in the embodiment of the present invention. ４０１～４０４は、本発明の実施例における試験結果を示す図である。 Reference numerals 401 to 404 show test results in the example of the present invention. ５０１～５０５は、本発明の実施例における試験結果を示す図である。501 to 505 are diagrams showing test results in the examples of the present invention. ６０１および６０２は、本発明の実施例における試験結果を示す図である。601 and 602 are diagrams showing test results in the example of the present invention.
　本発明の一実施形態について説明すると以下の通りであるが、本発明はこれに限定されない。本発明は、以下に説明する各構成に限定されるものではなく、特許請求の範囲に示した範囲で種々の変更が可能であり、異なる実施形態および実施例にそれぞれ開示された技術的手段を適宜組み合わせて得られる実施形態および実施例についても本発明の技術的範囲に含まれる。また、本明細書中に記載された文献の全てが、本明細書中において参考文献として援用される。本明細書中、数値範囲に関して「Ａ～Ｂ」と記載した場合、当該記載は「Ａ以上Ｂ以下」を意図する。 説明 One embodiment of the present invention will be described below, but the present invention is not limited to this. The present invention is not limited to each configuration described below, and various modifications are possible within the scope shown in the claims, and technical means disclosed in different embodiments and examples, respectively. Embodiments and examples obtained by appropriately combining are also included in the technical scope of the present invention. In addition, all of the documents described in this specification are incorporated herein by reference. In the present specification, when "AB" is described with respect to a numerical range, the description intends "A or more and B or less".
　〔１．本発明の原理〕
　図１に、本発明の一実施形態に係る電極構造体を示す。なお、当該電極構造体は、物質移動装置、物質検出装置、または、物質同定装置などとして利用可能である。 [1. Principle of the present invention)
FIG. 1 shows an electrode structure according to an embodiment of the present invention. Note that the electrode structure can be used as a substance transfer device, a substance detection device, a substance identification device, or the like.
　当該電極構造体は、流路１と、負極２および正極３からなる電極対と、を備えている。流路１に設けられている貫通孔には溶媒（例えば、水）が満たされており、当該溶媒中を検出対象である物質が移動する。 The electrode structure includes a flow path 1 and an electrode pair including a negative electrode 2 and a positive electrode 3. The through hole provided in the flow path 1 is filled with a solvent (for example, water), and the substance to be detected moves in the solvent.
　電極対にて電界を形成すれば、貫通孔を介して、電極対の間にイオン電流が流れる。また、当該電界によって、物質が貫通孔の中を移動する。貫通孔の中に物質が存在しているときと、貫通孔の中に物質が存在していないときとでは、負極２と正極３との間に流れるイオン電流の大きさが異なる。より具体的に、貫通孔の中に物質が存在していると、当該物質がイオン電流を遮り、負極２と正極３との間に流れるイオン電流が小さくなる。それ故に、イオン電流の変化を電流計４によって検出することにより、貫通孔内を通過する物質を検出、または、同定することができる。 れ ば If an electric field is formed by the electrode pairs, an ionic current flows between the electrode pairs via the through holes. In addition, the substance moves in the through hole by the electric field. The magnitude of the ionic current flowing between the negative electrode 2 and the positive electrode 3 differs between when the substance is present in the through hole and when no substance is present in the through hole. More specifically, when a substance is present in the through hole, the substance blocks the ionic current, and the ionic current flowing between the negative electrode 2 and the positive electrode 3 decreases. Therefore, a substance passing through the through-hole can be detected or identified by detecting a change in the ionic current with the ammeter 4.
　図２に、図１の破線にて囲った領域における、流路１の壁面の詳細な構造を示す。図２の２０１は、本発明の一実施形態に係る流路１の壁面を示す図であり、図２の２０２は、従来技術の流路の壁面を示す図である。 FIG. 2 shows the detailed structure of the wall surface of the flow channel 1 in a region surrounded by a broken line in FIG. 2 is a diagram showing a wall surface of the flow channel 1 according to an embodiment of the present invention, and 202 of FIG. 2 is a diagram showing a wall surface of a conventional flow channel.
　図２の２０１の矢印の左側に示すように、基材１０を被膜層２０にて覆わない場合には、溶媒が基材１０の表面と接触し、基材１０の溶媒と接触した側の表面に電荷が生じる。図２の２０１の矢印の右側に示すように、本発明の一実施形態に係る流路１では、基材１０を、原子層を含んでいる被膜層２０にて覆っている。原子層は、非常に薄い層であって、溶媒が容易に原子層の中に侵入することができる。原子層の中に侵入した溶媒は基材１０の表面と接触し、基材１０の溶媒と接触した側の表面に、基材１０を被膜層２０にて覆わない場合と同様に電荷が生じる。また、原子層は自身の表面に電荷を有しているので、被膜層２０の表面にも電荷が生じる。それ故に、本発明の一実施形態に係る流路１であれば、被膜層２０の表面電荷と、基材１０の表面電荷との２種類の電荷によって、流路１（換言すれば、貫通孔の壁面）の表面電荷を精密に制御することができる。 As shown on the left side of the arrow 201 in FIG. 2, when the base material 10 is not covered with the coating layer 20, the solvent contacts the surface of the base material 10, and the surface of the base material 10 on the side in contact with the solvent. Generates electric charge. As shown on the right side of the arrow 201 in FIG. 2, in the flow channel 1 according to the embodiment of the present invention, the base material 10 is covered with the coating layer 20 including the atomic layer. The atomic layer is a very thin layer so that the solvent can easily penetrate into the atomic layer. The solvent that has penetrated into the atomic layer comes into contact with the surface of the substrate 10, and a charge is generated on the surface of the substrate 10 on the side in contact with the solvent, as in the case where the substrate 10 is not covered with the coating layer 20. Further, since the atomic layer has a charge on its own surface, a charge is also generated on the surface of the coating layer 20. Therefore, in the case of the flow channel 1 according to one embodiment of the present invention, the flow channel 1 (in other words, the through-hole) is formed by two kinds of charges, the surface charge of the coating layer 20 and the surface charge of the substrate 10. The surface charge of the wall surface can be precisely controlled.
　流路１の表面電荷を精密に制御することができれば、例えば、（ｉ）物質と流路１の壁面との間のクーロン相互作用を弱くすること、および／または、（ｉｉ）流路１の壁面の近傍を流れ、かつ、物質の移動を妨げる電気浸透流を弱くすること、が可能になる。これらの制御が可能になれば、物質が貫通孔を通過し易くなる。物質が貫通孔を通過し易くなれば、微量の物質を含むサンプルであっても、当該サンプルを濃縮することなく、解析（例えば、当該サンプル中の物質を検出、または、同定）することができる。 If the surface charge of the flow path 1 can be precisely controlled, for example, (i) weakening the Coulomb interaction between the substance and the wall surface of the flow path 1 and / or (ii) It becomes possible to weaken the electroosmotic flow which flows near the wall surface and hinders the movement of the substance. If these controls become possible, it becomes easier for the substance to pass through the through-hole. If the substance easily passes through the through-hole, it is possible to analyze (for example, detect or identify a substance in the sample) without concentrating the sample even a sample containing a trace amount of the substance. .
　一方、図２の２０２に、基材１０と被膜層２０とを備えている従来技術の流路を示す。図２の２０２の矢印の右側に示すように従来技術の流路では、基材１０を、原子層を含んでいない被膜層２０にて覆っている。このような被膜層２０は、化学気層蒸着法、または、分子修飾などによって形成されるので、非常に厚い層である。このような非常に厚い被膜層２０の中には、溶媒が侵入することができない。それ故に、従来技術の流路では、基材１０の表面に電荷が生じない。従来技術の流路では被膜層２０の表面電荷のみによって流路（換言すれば、貫通孔の壁面）の表面電荷を制御することになるので、流路（換言すれば、貫通孔の壁面）の表面電荷を精密に制御することができない。 On the other hand, reference numeral 202 in FIG. 2 shows a conventional flow path including the base material 10 and the coating layer 20. As shown on the right side of the arrow 202 in FIG. 2, in the conventional flow path, the base material 10 is covered with the coating layer 20 containing no atomic layer. Such a coating layer 20 is a very thick layer because it is formed by a chemical vapor deposition method, molecular modification, or the like. The solvent cannot penetrate into such a very thick coating layer 20. Therefore, no charge is generated on the surface of the base material 10 in the conventional flow path. In the flow path of the prior art, the surface charge of the flow path (in other words, the wall surface of the through hole) is controlled only by the surface charge of the coating layer 20, so that the flow path (in other words, the wall surface of the through hole) is controlled. The surface charge cannot be precisely controlled.
　〔２．流路、および、流路の製造方法〕
　本実施の形態の流路は、物質が移動する経路である貫通孔が設けられている基材と、上記貫通孔の壁面上に設けられている、原子層を含んでいる被膜層と、を備えているものである。 [2. Channel, and a method of manufacturing the channel]
The flow channel of the present embodiment includes a base material provided with a through hole that is a path through which a substance moves, and a coating layer including an atomic layer, which is provided on a wall surface of the through hole. It has something.
　本明細書にて「原子層」とは、特定の原子が平面的に並んで形成されている層であって、当該層の厚さが、特定の原子１個分の厚さである層、を意図する。 As used herein, the term “atomic layer” refers to a layer in which specific atoms are formed in a plane, and the layer has a thickness of one specific atom. Intended.
　上記物質は、例えば、検出対象または同定対象である物質であり得る。上記物質としては、例えば、原子、分子、ポリマー、または、これらの複合体を挙げることができる。更に具体的に、上記物質としては、核酸（ＤＮＡまたはＲＮＡ）、アミノ酸、タンパク質、花粉、ウイルス、菌類、細胞、有機粒子、または、無機粒子を挙げることができる。 The substance may be, for example, a substance to be detected or identified. Examples of the substance include an atom, a molecule, a polymer, and a complex thereof. More specifically, examples of the substance include nucleic acids (DNA or RNA), amino acids, proteins, pollen, viruses, fungi, cells, organic particles, and inorganic particles.
　上記貫通孔内には、所望の溶媒、または、溶媒を含むゲルが満たされ得る。上記溶媒としては、例えば、水、ＴＥバッファー（Ｔｒｉｓ－ＨＣｌ、ＥＤＴＡバッファー）、および、塩化物（例えば、ＫＣｌ、ＬｉＣｌまたはＮａＣｌ）を含有する水溶液を挙げることができる。上記ゲルとしては、例えば、ポリアクリルアミドゲル、アガロースゲル、デキストラン、および、ポリエチレングレコールを挙げることができる。上記溶媒は、電解質を含んでいてもよい。上記電解質としては、電解質としては、例えば、ＫＣｌ、ＮａＣｌ、および、ＬｉＣｌを挙げることができる。 所 望 A desired solvent or a gel containing a solvent can be filled in the through-hole. Examples of the solvent include an aqueous solution containing water, TE buffer (Tris-HCl, EDTA buffer), and chloride (eg, KCl, LiCl, or NaCl). Examples of the gel include polyacrylamide gel, agarose gel, dextran, and polyethylene glycol. The solvent may include an electrolyte. Examples of the electrolyte include KCl, NaCl, and LiCl.
　上記流路は、物質が移動する経路である貫通孔が設けられている基材を備えている。なお、基材自体の形状は、特に限定されず、板状であってもよいし、柱状であってもよい。 The flow path includes a base material provided with a through-hole, which is a path through which a substance moves. In addition, the shape of the base material itself is not particularly limited, and may be a plate shape or a column shape.
　基材の材料は、特に限定されず、例えば、窒化シリコン、二酸化ケイ素、金属、酸化亜鉛、二酸化チタン、酸化ハフニウム、および、アルミナを挙げることができる。良好な生体適合性が得られるという有利な効果を奏することから、これらの材料の中では、アルミナが好ましい。 材料 The material of the base material is not particularly limited, and examples thereof include silicon nitride, silicon dioxide, metal, zinc oxide, titanium dioxide, hafnium oxide, and alumina. Among these materials, alumina is preferred because of the advantageous effect of obtaining good biocompatibility.
　貫通孔の形状は、特に限定されず、例えば、円柱、または、多角柱であり得る。貫通孔の形状が円柱、または、多角柱である場合、当該円柱の底面の円の直径、および、当該多角柱の底面の外接円の直径は、特に限定されず、移動する物質の大きさに応じて、適宜、設定され得る。円の直径Ａ、および、外接円の直径Ａは、例えば、０．１ｎｍ～１００μｍ、０．１ｎｍ～１０μｍ、０．１ｎｍ～１μｍ、０．１ｎｍ～１００ｎｍ、０．１ｎｍ～１０ｎｍ、または、１ｎｍ～１０ｎｍであってもよい。 形状 The shape of the through-hole is not particularly limited, and may be, for example, a cylinder or a polygonal pillar. If the shape of the through-hole is a cylinder, or a polygonal pillar, the diameter of the circle at the bottom of the cylinder, and the diameter of the circumscribed circle at the bottom of the polygonal pillar are not particularly limited, and may vary depending on the size of the moving substance. Accordingly, it can be set appropriately. The diameter A of the circle and the diameter A of the circumscribed circle are, for example, 0.1 nm to 100 μm, 0.1 nm to 10 μm, 0.1 nm to 1 μm, 0.1 nm to 100 nm, 0.1 nm to 10 nm, or 1 nm to 100 nm. It may be 10 nm.
　貫通孔の深さＢは、特に限定されず、例えば、０．１ｎｍ～１００μｍ、０．１ｎｍ～１０μｍ、０．１ｎｍ～１μｍ、０．１ｎｍ～１００ｎｍ、０．１ｎｍ～１０ｎｍ、または、１ｎｍ～１０ｎｍであってもよい。 The depth B of the through hole is not particularly limited, and is, for example, 0.1 nm to 100 μm, 0.1 nm to 10 μm, 0.1 nm to 1 μm, 0.1 nm to 100 nm, 0.1 nm to 10 nm, or 1 nm to 10 nm. It may be.
　貫通孔のアスペクト比（深さＢ／直径Ａ）は、特に限定されず、例えば、１／１０００～１／１、１／１００～１／１、または、１／１０～１／１であってもよい。ナノポアセンサの空間分解能が向上するという有利な効果を奏することから、貫通孔のアスペクト比は、小さいほど好ましい。 The aspect ratio (depth B / diameter A) of the through-hole is not particularly limited, and is, for example, 1/1000 to 1/1, 1/100 to 1/1, or 1/10 to 1/1. Is also good. Since the advantageous effect that the spatial resolution of the nanopore sensor is improved is obtained, the smaller the aspect ratio of the through hole, the more preferable.
　貫通孔を移動する物質の大きさは特に限定されないが、当該物質の最大幅Ｃと上記直径Ａとの長さの比Ｒ＝Ｃ／Ａ[無次元]は、０．５０＜Ｃ／Ａ＜１の関係を満たすことが好ましく、０．６０＜Ｃ／Ａ＜１の関係を満たすことが更に好ましく、０．６５＜Ｃ／Ａ＜１の関係を満たすことが更に好ましく、０．７０＜Ｃ／Ａ＜１の関係を満たすことが更に好ましく、０．８０＜Ｃ／Ａ＜１の関係を満たすことが更に好ましく、０．９０＜Ｃ／Ａ＜１の関係を満たすことが更に好ましく、０．９５＜Ｃ／Ａ＜１の関係を満たすことが最も好ましい。 The size of the substance moving through the through-hole is not particularly limited, but the ratio R = C / A [dimension] of the maximum width C of the substance to the diameter A is 0.50 <C / A <. 1 preferably, more preferably 0.60 <C / A <1, more preferably 0.65 <C / A <1, and 0.70 <C. / A <1 is more preferably satisfied, the relationship 0.80 <C / A <1 is more preferably satisfied, and the relationship 0.90 <C / A <1 is more preferably satisfied. Most preferably, the relationship of .95 <C / A <1 is satisfied.
　上記構成によれば、貫通孔を物質が通過するときに、イオン電流の大半を妨げることができる。換言すれば、上記構成によれば、貫通孔を物質が通過していないときに当該貫通孔を流れるイオン電流と、貫通孔を物質が通過しているときに当該貫通孔を流れるイオン電流との差が大きくなる。それ故に、本実施の形態の流路を物質検出装置、または、物質同定装置に用いたときに、物質の検出感度、または、物質の同定精度を高めることができる。 According to the above configuration, most of the ion current can be prevented when the substance passes through the through-hole. In other words, according to the above configuration, the ionic current flowing through the through-hole when the substance does not pass through the through-hole and the ionic current flowing through the through-hole when the substance passes through the through-hole. The difference increases. Therefore, when the channel according to the present embodiment is used for a substance detection device or a substance identification device, the detection sensitivity of the substance or the identification accuracy of the substance can be improved.
　貫通孔の壁面上には、原子層を含んでいる被膜層が設けられている。なお、被膜層は、貫通孔の壁面上のみならず、基材全体の上に設けられていてもよい。当該被膜層は、原子層、または、原子層の積層体を含んでいるものであってもよいし、原子層、または、原子層の積層体からなるものであってもよい。 被膜 A coating layer including an atomic layer is provided on the wall surface of the through hole. Note that the coating layer may be provided not only on the wall surface of the through hole but also on the entire base material. The coating layer may include an atomic layer or a stack of atomic layers, or may be an atomic layer or a stack of atomic layers.
　原子層は、（ｉ）貫通孔内を電気泳動する物質が「－」の電荷を有する場合には、「－」の電荷を有し、貫通孔内を電気泳動する物質が「＋」の電荷を有する場合には「＋」の電荷を有する原子層であって、かつ、（ｉｉ）ζ電位の値が小さい原子層であることが好ましい。なお、ζ電位の値は、小さいほど好ましい。当該構成であれば、物質が、貫通孔内を電気泳動し易くなる。ζ電位の値は、原子層の厚さを調節することによって、調節され得る（例えば、後述する実施例の図４など参照）。原子層の厚さをより正確に調節するという観点からは、原子層堆積法（Atomic Layer Deposition：ＡＬＤ）によって原子層を形成することが好ましい。 The atomic layer has (i) a charge of “−” when the substance that electrophoreses in the through hole has a “−” charge, and a charge of “+” when the substance electrophoreses in the through hole. In the case of having an atomic layer, it is preferable that the atomic layer has an electric charge of “+” and (ii) the atomic layer has a small value of ζ potential. Note that the value of the ζ potential is preferably as small as possible. With such a configuration, the substance is easily electrophoresed in the through hole. The value of the ζ potential can be adjusted by adjusting the thickness of the atomic layer (for example, see FIG. 4 of an embodiment described later). From the viewpoint of more accurately adjusting the thickness of the atomic layer, it is preferable to form the atomic layer by an atomic layer deposition method (Atomic Layer Deposition: ALD).
　原子層を構成する物質としては、特に限定されず、例えば、Ａｌ２Ｏ３、ＨｆＯ２、ＴｉＯ２、ＺｎＯ、および、ＳｉＯ２を挙げることができる。これらの物質を用いれば、原子層の厚さを、所望の厚さに容易に調節することができる。良好な生体適合性が得られるという有利な効果を奏することから、これらの物質の中では、Ａｌ２Ｏ３が好ましい。 The material constituting the atomic layer is not particularly limited, and examples thereof include Al 2 O 3 , HfO 2 , TiO 2 , ZnO, and SiO 2 . By using these substances, the thickness of the atomic layer can be easily adjusted to a desired thickness. Among these substances, Al 2 O 3 is preferable because it has an advantageous effect of obtaining good biocompatibility.
　被膜層の厚さは、原子層の厚さの２００倍以下であることが好ましいが、１９０倍以下、１８０倍以下、１７０倍以下、１６０倍以下、１５０倍以下、１４０倍以下、１３０倍以下、１２０倍以下、１１０倍以下、１００倍以下、９０倍以下、８０倍以下、７０倍以下、６０倍以下、５０倍以下、４０倍以下、３０倍以下、２０倍以下、または、１０倍以下であってもよい。一方、被膜層の厚さの下限は、特に限定されないが、原子層の厚さの１倍、２倍、３倍、４倍、または、５倍であってもよい。上記構成であれば、溶媒が基材の表面と容易に接触することができ、その結果、基材の表面に安定して所望の電荷を生じさせることができる。 The thickness of the coating layer is preferably 200 times or less the thickness of the atomic layer, but is 190 times or less, 180 times or less, 170 times or less, 160 times or less, 150 times or less, 140 times or less, 130 times or less. 120 times or less, 110 times or less, 100 times or less, 90 times or less, 80 times or less, 70 times or less, 60 times or less, 50 times or less, 40 times or less, 30 times or less, 20 times or less, or 10 times or less It may be. On the other hand, the lower limit of the thickness of the coating layer is not particularly limited, but may be 1, 2, 3, 4, or 5 times the thickness of the atomic layer. With the above configuration, the solvent can easily come into contact with the surface of the substrate, and as a result, a desired charge can be stably generated on the surface of the substrate.
　上述したように、被膜層は、原子層の積層体を含んでいるものであってもよいし、原子層の積層体からなるものであってもよい。被膜層は、例えば、（ｉ）２００層以下、１９０層以下、１８０層以下、１７０層以下、１６０層以下、１５０層以下、１４０層以下、１３０層以下、１２０層以下、１１０層以下、１００層以下、９０層以下、８０層以下、７０層以下、６０層以下、５０層以下、４０層以下、３０層以下、２０層以下、または、１０層以下の原子層を含んでいるものであってもよいし、（ｉｉ）２００層以下、１９０層以下、１８０層以下、１７０層以下、１６０層以下、１５０層以下、１４０層以下、１３０層以下、１２０層以下、１１０層以下、１００層以下、９０層以下、８０層以下、７０層以下、６０層以下、５０層以下、４０層以下、３０層以下、２０層以下、または、１０層以下の原子層からなるものであってもよい。このとき、被膜層を構成する原子層の数の下限は、特に限定されず、例えば、１層、２層、３層、４層、または、５層であってもよい。 As described above, the coating layer may include a stacked body of atomic layers, or may be formed of a stacked body of atomic layers. The coating layer is, for example, (i) 200 or less, 190 or less, 180 or less, 170 or less, 160 or less, 150 or less, 140 or less, 130 or less, 120 or less, 110 or less, 100 or less It has at most 90, up to 90, at most 80, at most 70, at most 60, at most 50, at most 40, at most 30, at most 20, at most 20, and at most 10 atomic layers. (Ii) 200 layers or less, 190 layers or less, 180 layers or less, 170 layers or less, 160 layers or less, 150 layers or less, 140 layers or less, 130 layers or less, 120 layers or less, 110 layers or less, 100 layers Hereinafter, it may be composed of 90 or less, 80 or less, 70 or less, 60 or less, 50 or less, 40 or less, 30 or less, 20 or less, or 10 or less atomic layers. . At this time, the lower limit of the number of atomic layers constituting the coating layer is not particularly limited, and may be, for example, one layer, two layers, three layers, four layers, or five layers.
　原子層を構成する物質に応じて、原子層の厚さは決まっており、当該厚さは周知である（例えば、文献Rev. Sci. Instrum. 73, 2981-2987 （2002）を参照）。当該文献は、本明細書中において参考文献として援用される。 厚 The thickness of the atomic layer is determined according to the material constituting the atomic layer, and the thickness is well known (see, for example, literature Rev. {Sci.} Instrum. {73, {2981-2987} (2002)). This reference is incorporated herein by reference.
　本実施の形態の流路の製造方法は、基材に設けられている、物質が移動する経路である貫通孔の壁面上に、原子層を含んでいる被膜層を形成する被膜層形成工程を有している。 The method for manufacturing a channel according to the present embodiment includes a coating layer forming step of forming a coating layer including an atomic layer on a wall surface of a through-hole that is provided on a base material and that is a path through which a substance moves. Have.
　被膜層形成工程において、被膜層に含まれる原子層を形成する方法としては、周知の原子層堆積法（Atomic Layer Deposition：ＡＬＤ）を挙げることができる。原子堆積法によって原子層を形成すれば、所望の数の原子層を正確に形成することができる。 (4) In the film layer forming step, as a method of forming an atomic layer included in the film layer, a known atomic layer deposition method (Atomic Layer Deposition: ALD) can be mentioned. If an atomic layer is formed by an atomic deposition method, a desired number of atomic layers can be accurately formed.
　〔３．電極構造体、および、電極構造体の製造方法〕
　本実施の形態の電極構造体は、（ｉ）物質が移動する経路である貫通孔が設けられている基材と、上記貫通孔の壁面上に設けられている、原子層を含んでいる被膜層と、を備えている流路と、（ｉｉ）上記貫通孔を挟むように配置されている電極対と、を備えているものである。 [3. Electrode structure and method for manufacturing electrode structure]
The electrode structure according to the present embodiment includes (i) a base material provided with a through-hole as a path through which a substance moves, and a coating including an atomic layer provided on a wall surface of the through-hole. And (ii) an electrode pair disposed so as to sandwich the through hole.
　上記流路の具体的な構成については、既に説明したので、ここではその説明を省略する。また、上記電極対としては、特に限定されず、適宜、周知の電極対（例えば、銀／塩化銀（Ａｇ／ＡｇＣｌ）電極）を用いればよい。 具体 Since the specific configuration of the flow channel has already been described, the description is omitted here. The electrode pair is not particularly limited, and a well-known electrode pair (for example, a silver / silver chloride (Ag / AgCl) electrode) may be appropriately used.
　被膜層の厚さは、原子層の厚さの２００倍以下であることが好ましいが、１９０倍以下、１８０倍以下、１７０倍以下、１６０倍以下、１５０倍以下、１４０倍以下、１３０倍以下、１２０倍以下、１１０倍以下、１００倍以下、９０倍以下、８０倍以下、７０倍以下、６０倍以下、５０倍以下、４０倍以下、３０倍以下、２０倍以下、または、１０倍以下であってもよい。一方、被膜の厚さの下限は、特に限定されないが、原子層の厚さの１倍、２倍、３倍、４倍、または、５倍であってもよい。上記構成であれば、溶媒が基材の表面と容易に接触することができ、その結果、基材の表面に安定して所望の電荷を生じさせることができる。上述したように、被膜層は、原子層の積層体を含んでいるものであってもよいし、原子層の積層体からなるものであってもよい。被膜層を構成する原子層の数については、既に説明したので、ここではその説明を省略する。 The thickness of the coating layer is preferably 200 times or less the thickness of the atomic layer, but is 190 times or less, 180 times or less, 170 times or less, 160 times or less, 150 times or less, 140 times or less, 130 times or less. 120 times or less, 110 times or less, 100 times or less, 90 times or less, 80 times or less, 70 times or less, 60 times or less, 50 times or less, 40 times or less, 30 times or less, 20 times or less, or 10 times or less It may be. On the other hand, the lower limit of the thickness of the coating is not particularly limited, but may be 1, 2, 3, 4, or 5 times the thickness of the atomic layer. With the above configuration, the solvent can easily come into contact with the surface of the substrate, and as a result, a desired charge can be stably generated on the surface of the substrate. As described above, the coating layer may include a stacked body of atomic layers, or may be formed of a stacked body of atomic layers. Since the number of the atomic layers constituting the coating layer has already been described, the description thereof is omitted here.
　本実施の形態の電極構造体の製造方法は、基材に設けられている、物質が移動する経路である貫通孔の壁面上に、原子層を含んでいる被膜層を形成する被膜層形成工程と、上記貫通孔を挟むように電極対を設ける電極対形成工程と、を有している。 The method for manufacturing an electrode structure according to the present embodiment includes a coating layer forming step of forming a coating layer including an atomic layer on a wall surface of a through hole provided in a base material, which is a path through which a substance moves. And an electrode pair forming step of providing an electrode pair so as to sandwich the through hole.
　被膜層形成工程において、被膜層に含まれる原子層を形成する方法としては、周知の原子層堆積法（Atomic Layer Deposition：ＡＬＤ）を挙げることができる。原子堆積法によって原子層を形成すれば、所望の数の原子層を正確に形成することができる。 (4) In the film layer forming step, as a method of forming an atomic layer included in the film layer, a known atomic layer deposition method (Atomic Layer Deposition: ALD) can be mentioned. If an atomic layer is formed by an atomic deposition method, a desired number of atomic layers can be accurately formed.
　電極対形成工程において、電極対を設ける具体的な方法は限定されず、貫通孔を挟むように電極対を設ければよい。 に お い て In the electrode pair forming step, a specific method of providing the electrode pair is not limited, and the electrode pair may be provided so as to sandwich the through hole.
　上記被膜層形成工程では、原子層の厚さの２００倍以下の厚さになるように被膜層が形成されることが好ましい。被膜層の厚さは、１９０倍以下、１８０倍以下、１７０倍以下、１６０倍以下、１５０倍以下、１４０倍以下、１３０倍以下、１２０倍以下、１１０倍以下、１００倍以下、９０倍以下、８０倍以下、７０倍以下、６０倍以下、５０倍以下、４０倍以下、３０倍以下、２０倍以下、または、１０倍以下であってもよい。一方、被膜層の厚さの下限は、特に限定されないが、原子層の厚さの１倍、２倍、３倍、４倍、または、５倍であってもよい。上記構成であれば、溶媒が基材の表面と容易に接触することができ、その結果、基材の表面に安定して所望の電荷を生じさせることができる。上述したように、被膜層は、原子層の積層体を含んでいるものであってもよいし、原子層の積層体からなるものであってもよい。被膜層を構成する原子層の数については、既に説明したので、ここではその説明を省略する。 で は In the above-mentioned coating layer forming step, it is preferable that the coating layer is formed so as to have a thickness of 200 times or less the thickness of the atomic layer. The thickness of the coating layer is 190 times or less, 180 times or less, 170 times or less, 160 times or less, 150 times or less, 140 times or less, 130 times or less, 120 times or less, 110 times or less, 100 times or less, 90 times or less. , 80 times or less, 70 times or less, 60 times or less, 50 times or less, 40 times or less, 30 times or less, 20 times or less, or 10 times or less. On the other hand, the lower limit of the thickness of the coating layer is not particularly limited, but may be 1, 2, 3, 4, or 5 times the thickness of the atomic layer. With the above configuration, the solvent can easily come into contact with the surface of the substrate, and as a result, a desired charge can be stably generated on the surface of the substrate. As described above, the coating layer may include a stacked body of atomic layers, or may be formed of a stacked body of atomic layers. Since the number of the atomic layers constituting the coating layer has already been described, the description thereof is omitted here.
　〔４．その他〕
　本発明は、以下のように構成することができる。 [4. Others)
The present invention can be configured as follows.
　本発明の一態様に係る流路は、物質が移動する経路である貫通孔が設けられている基材と、上記貫通孔の壁面上に設けられている、原子層を含んでいる被膜層と、を備えていることを特徴としている。 The flow channel according to one embodiment of the present invention is provided with a base material provided with a through hole that is a path through which a substance moves, and a coating layer including an atomic layer, which is provided on a wall surface of the through hole. , Are provided.
　原子層を含んでいる被膜層は、自身の表面に電荷を有している。また、原子層は、非常に薄い層であって、流路中に満たされる溶媒（例えば、水）が容易に原子層の中に侵入することができる。原子層の中に侵入した溶媒は基材の表面と接触し、基材の表面に電荷が生じる。それ故に、上記構成であれば、原子層を含んでいる被膜層の表面電荷と、基材の表面電荷との２種類の電荷によって、貫通孔の壁面の表面電荷を精密に制御することができる。 被膜 The coating layer including the atomic layer has a charge on its surface. Further, the atomic layer is a very thin layer, and a solvent (eg, water) filled in the flow path can easily enter the atomic layer. The solvent that has penetrated into the atomic layer comes into contact with the surface of the substrate, and charges are generated on the surface of the substrate. Therefore, with the above configuration, the surface charge on the wall surface of the through-hole can be precisely controlled by two kinds of charges, the surface charge of the coating layer including the atomic layer and the surface charge of the base material. .
　本発明の一態様に係る流路では、上記被膜層の厚さは、上記原子層の厚さの２００倍以下であることが好ましい。 で は In the flow channel according to one embodiment of the present invention, the thickness of the coating layer is preferably 200 times or less the thickness of the atomic layer.
　上記構成であれば、被膜層が薄いので、溶媒が基材の表面と容易に接触することができる。その結果、基材の表面に、安定して電荷を生じさせることができる。 で あ れ ば With the above configuration, since the coating layer is thin, the solvent can easily contact the surface of the substrate. As a result, charges can be stably generated on the surface of the base material.
　本発明の一態様に係る流路では、上記原子層は、Ａｌ２Ｏ３、ＨｆＯ２、ＴｉＯ２、ＺｎＯ、または、ＳｉＯ２の原子層であることが好ましい。 In the channel according to one embodiment of the present invention, the atomic layer is preferably an atomic layer of Al 2 O 3 , HfO 2 , TiO 2 , ZnO, or SiO 2 .
　上記構成であれば、原子層の厚さを、所望の厚さに容易に調節することができる。 で あ れ ば With the above configuration, the thickness of the atomic layer can be easily adjusted to a desired thickness.
　本発明の一態様に係る電極構造体は、本発明の一態様に係る流路と、上記貫通孔を挟むように配置されている電極対と、を備えていることを特徴としている。 電極 An electrode structure according to one embodiment of the present invention includes the channel according to one embodiment of the present invention, and an electrode pair arranged so as to sandwich the through hole.
　電極対によって電界を形成すれば、貫通孔を介して、電極対の間にイオン電流が流れる。また、当該電界によって、物質が貫通孔の中を移動する。貫通孔の中に物質が存在しているときと、貫通孔の中に物質が存在していないときとでは、イオン電流の大きさが異なる。それ故に、イオン電流の変化を検出することによって、物質を検出することができる。貫通孔の壁面の表面電荷は精密に制御されているので、物質は容易に貫通孔の中を移動することができ、その結果、物質を精度高く検出することができる。 れ ば If an electric field is formed by the electrode pairs, an ionic current flows between the electrode pairs via the through holes. In addition, the substance moves in the through hole by the electric field. The magnitude of the ionic current differs between when a substance is present in the through hole and when no substance is present in the through hole. Therefore, a substance can be detected by detecting a change in the ion current. Since the surface charge on the wall surface of the through hole is precisely controlled, the substance can easily move through the through hole, and as a result, the substance can be detected with high accuracy.
　本発明の一態様に係る流路の製造方法は、基材に設けられている、物質が移動する経路である貫通孔の壁面上に、原子層を含んでいる被膜層を形成する被膜層形成工程を有していることを特徴としている。 The method for manufacturing a flow channel according to one embodiment of the present invention includes forming a coating layer including an atomic layer on a wall surface of a through-hole provided in a base material, which is a path through which a substance moves. It is characterized by having a process.
　原子層を含んでいる被膜層は、自身の表面に電荷を有している。また、原子層は、非常に薄い層であって、流路中に満たされる溶媒（例えば、水）が容易に原子層の中に侵入することができる。原子層の中に侵入した溶媒は基材の表面と接触し、基材の表面に電荷が生じる。それ故に、上記構成であれば、原子層を含んでいる被膜層の表面電荷と、基材の表面電荷との２種類の電荷によって、貫通孔の壁面の表面電荷を精密に制御することができる。 被膜 The coating layer including the atomic layer has a charge on its surface. Further, the atomic layer is a very thin layer, and a solvent (eg, water) filled in the flow path can easily enter the atomic layer. The solvent that has penetrated into the atomic layer comes into contact with the surface of the substrate, and charges are generated on the surface of the substrate. Therefore, with the above configuration, the surface charge on the wall surface of the through-hole can be precisely controlled by two kinds of charges, the surface charge of the coating layer including the atomic layer and the surface charge of the base material. .
　本発明の一態様に係る流路の製造方法では、上記被膜層形成工程では、上記原子層の厚さの２００倍以下の厚さになるように上記被膜層が形成されることが好ましい。 In the method of manufacturing a flow channel according to one embodiment of the present invention, it is preferable that, in the coating layer forming step, the coating layer is formed so as to have a thickness of 200 times or less the thickness of the atomic layer.
　上記構成であれば、被膜層が薄いので、溶媒が基材の表面と容易に接触することができる。その結果、基材の表面に、安定して電荷を生じさせることができる。 で あ れ ば With the above configuration, since the coating layer is thin, the solvent can easily contact the surface of the substrate. As a result, charges can be stably generated on the surface of the base material.
　本発明の一態様に係る流路の製造方法では、上記原子層は、Ａｌ２Ｏ３、ＨｆＯ２、ＴｉＯ２、ＺｎＯ、または、ＳｉＯ２の原子層であることが好ましい。 In the method for manufacturing a channel according to one embodiment of the present invention, the atomic layer is preferably an atomic layer of Al 2 O 3 , HfO 2 , TiO 2 , ZnO, or SiO 2 .
　上記構成であれば、原子層の厚さを、所望の厚さに容易に調節することができる。 で あ れ ば With the above configuration, the thickness of the atomic layer can be easily adjusted to a desired thickness.
　本発明の一態様に係る流路の製造方法では、上記被膜層形成工程では、原子層堆積法によって上記原子層を形成することが好ましい。 In the method for manufacturing a flow channel according to one embodiment of the present invention, it is preferable that, in the coating layer forming step, the atomic layer is formed by an atomic layer deposition method.
　上記構成であれば、原子層の厚さを、所望の厚さに容易、かつ、正確に調節することができる。 With the above configuration, the thickness of the atomic layer can be easily and accurately adjusted to a desired thickness.
　本発明の一態様に係る電極構造体の製造方法は、基材に設けられている、物質が移動する経路である貫通孔の壁面上に、原子層を含んでいる被膜層を形成する被膜層形成工程と、上記貫通孔を挟むように電極対を設ける電極対形成工程と、を有することを特徴としている。 According to one embodiment of the present invention, there is provided a method for manufacturing an electrode structure, comprising: forming a coating layer containing an atomic layer on a wall surface of a through-hole provided in a substrate, which is a path through which a substance moves. The method is characterized by including a forming step and an electrode pair forming step of providing an electrode pair so as to sandwich the through hole.
　電極対によって電界を形成すれば、貫通孔を介して、電極対の間にイオン電流が流れる。また、当該電界によって、物質が貫通孔の中を移動する。貫通孔の中に物質が存在しているときと、貫通孔の中に物質が存在していないときとでは、イオン電流の大きさが異なる。それ故に、イオン電流の変化を検出することによって、物質を検出することができる。貫通孔の壁面の表面電荷は精密に制御されているので、物質は容易に貫通孔の中を移動することができ、その結果、物質を精度高く検出することができる。 れ ば If an electric field is formed by the electrode pairs, an ionic current flows between the electrode pairs via the through holes. In addition, the substance moves in the through hole by the electric field. The magnitude of the ionic current differs between when a substance is present in the through hole and when no substance is present in the through hole. Therefore, a substance can be detected by detecting a change in the ion current. Since the surface charge on the wall surface of the through hole is precisely controlled, the substance can easily move through the through hole, and as a result, the substance can be detected with high accuracy.
　本発明の一態様に係る電極構造体の製造方法では、上記被膜層形成工程では、上記原子層の厚さの２００倍以下の厚さになるように上記被膜層が形成されることが好ましい。 In the method for manufacturing an electrode structure according to one embodiment of the present invention, it is preferable that, in the coating layer forming step, the coating layer is formed to have a thickness of 200 times or less the thickness of the atomic layer.
　上記構成であれば、被膜層が薄いので、溶媒が基材の表面と容易に接触することができる。その結果、基材の表面に、安定して電荷を生じさせることができる。 で あ れ ば With the above configuration, since the coating layer is thin, the solvent can easily contact the surface of the substrate. As a result, charges can be stably generated on the surface of the base material.
　本発明の一態様に係る電極構造体の製造方法では、上記原子層は、Ａｌ２Ｏ３、ＨｆＯ２、ＴｉＯ２、ＺｎＯ、または、ＳｉＯ２の原子層であることが好ましい。 In the method for manufacturing an electrode structure according to one embodiment of the present invention, the atomic layer is preferably an atomic layer of Al 2 O 3 , HfO 2 , TiO 2 , ZnO, or SiO 2 .
　上記構成であれば、原子層の厚さを、所望の厚さに容易に調節することができる。 で あ れ ば With the above configuration, the thickness of the atomic layer can be easily adjusted to a desired thickness.
　本発明の一態様に係る電極構造体の製造方法では、上記被膜層形成工程では、原子層堆積法によって上記原子層を形成することが好ましい。 で は In the method for manufacturing an electrode structure according to one embodiment of the present invention, it is preferable that, in the coating layer forming step, the atomic layer is formed by an atomic layer deposition method.
　上記構成であれば、原子層の厚さを、所望の厚さに容易、かつ、正確に調節することができる。 With the above configuration, the thickness of the atomic layer can be easily and accurately adjusted to a desired thickness.
　図３を参照しながら、以下の＜１＞～＜５＞にて、試験方法について説明し、以下の＜６＞～＜８＞にて、試験結果について説明する。 試 験 With reference to FIG. 3, the following <1> to <5> describe the test method, and the following <6> to <8> describe the test results.
　＜１．流路および電極構造体の作製＞
　Ｓｉ３Ｎ４層によって覆われたＳｉウエハーに対して、反応性イオン（エッチングガス：ＣＦ４）を用いたドライエッチングを施し、これによって、狭い領域のＳｉ３Ｎ４層を除去するとともに、当該Ｓｉ３Ｎ４層の下のＳｉウエハーを露出させた。 <1. Preparation of flow path and electrode structure>
The Si wafer covered with the Si 3 N 4 layer is subjected to dry etching using reactive ions (etching gas: CF 4 ), thereby removing the Si 3 N 4 layer in a narrow area, and exposing the Si wafer under the Si 3 N 4 layer.
　次いで、露出したＳｉウエハーを、ＫＯＨ水溶液中、１２０℃にて、深くエッチングすることによって、５０ｎｍの厚さのＳｉ３Ｎ４膜を形成した。当該Ｓｉ３Ｎ４膜の上に、スピンコートによって、電子ビームレジスト層（ＺＥＰ－５２０Ａ－７）を形成し、かつ、電子ビームリソグラフィーによって、直径１．２μｍの円を描いた。現像した後、ドライエッチングによってＳｉ３Ｎ４膜を削り、これによって、直径１．２μｍ、深さ５０ｎｍの貫通孔を形成した。 Next, the exposed Si wafer was deeply etched in a KOH aqueous solution at 120 ° C. to form a 50 nm thick Si 3 N 4 film. An electron beam resist layer (ZEP-520A-7) was formed on the Si 3 N 4 film by spin coating, and a circle having a diameter of 1.2 μm was drawn by electron beam lithography. After the development, the Si 3 N 4 film was shaved by dry etching, thereby forming a through hole having a diameter of 1.2 μm and a depth of 50 nm.
　次いで、貫通孔が形成されたＳｉウエハーを、一昼夜、Ｎ，Ｎ－ジメチルホルムアミド中に浸け、これによって、削りカスを除去した。Ｓｉウエハーをエタノールおよびアセトンを用いて洗浄した。その後、トリメチルアルミニウムおよび水前駆体（water precursors）を用いる、当標準的な原子層堆積法（Oxford Instruments）によって、該Ｓｉウエハーを、Ａｌ２Ｏ３層にて均一に覆った。Ａｌ２Ｏ３層を構成する原子層の厚さは、反応サイクルの数を制御することによって、０．１２ｎｍに正確に制御した。例えば、Ａｌ２Ｏ３層の厚さが、１ｎｍ、２ｎｍ、３ｎｍ、４ｎｍ、５ｎｍ、または、６ｎｍの場合、これらのＡｌ２Ｏ３層の各々の厚さは、原子層の厚さの８倍、１７倍、２５倍、３３倍、４２倍、または、５０倍となる。 Next, the Si wafer in which the through hole was formed was immersed in N, N-dimethylformamide all day and night, thereby removing shavings. The Si wafer was cleaned using ethanol and acetone. Then, using trimethylaluminum and water precursors (water Precursors), by those standard atomic layer deposition (Oxford Instruments), the Si wafer, uniformly covered with the Al 2 O 3 layer. The thickness of the atomic layer constituting the Al 2 O 3 layer was precisely controlled to 0.12 nm by controlling the number of reaction cycles. For example, if the thickness of the Al 2 O 3 layer is 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, or 6 nm, the thickness of each of these Al 2 O 3 layers is eight times the thickness of the atomic layer. , 17 times, 25 times, 33 times, 42 times, or 50 times.
　＜２．イオン電流の測定＞
　上述した＜１．流路および電極構造体の作製＞にて作製した貫通孔が形成されたＳｉウエハーを、ポリジメチルシロキサンによって形成されている２つのポリマーブロックによって、シールした。具体的には、初めに、貫通孔が形成されたＳｉウエハー、および、ポリマーブロックの各々の表面を、酸素プラズマによって活性化させた。次いで、貫通孔が形成されたＳｉウエハー、および、ポリマーブロックを組み合わせて、互いに結合した複合ブロックを作製した。 <2. Measurement of ion current>
<1. Fabrication of Channel and Electrode Structure>, the Si wafer having the through-hole formed therein was sealed with two polymer blocks formed of polydimethylsiloxane. Specifically, first, the surface of each of the Si wafer on which the through hole was formed and the polymer block was activated by oxygen plasma. Next, a composite block bonded to each other was produced by combining the Si wafer with the through-hole formed therein and the polymer block.
　ドリルを用いて、複合ブロックに３つの孔を形成した。２つの孔には、バッファーを注入し、残りの１つの孔には、貫通孔を介して流れるイオン電流を測定するためのＡｇ／ＡｇＣｌ電極を配置した。 孔 Using a drill, three holes were formed in the composite block. A buffer was injected into the two holes, and an Ag / AgCl electrode for measuring an ionic current flowing through the through hole was arranged in the other hole.
　イオン電流を測定する前に、貫通孔を挟んだ一方の側の空間を、粒子（直径が０．７８μｍである、カルボン酸塩化されたポリスチレン粒子（Thermo Scientific））が０．３ｐＭの濃度にて分散している０．１×ＰＢＳにて満たし、貫通孔を挟んだ他方の側の空間を、粒子が分散していない０．１×ＰＢＳにて満たした。 Before measuring the ionic current, the space on one side sandwiching the through-hole was filled with particles (carboxylated polystyrene particles (0.78 μm in diameter, Thermo Scientific)) at a concentration of 0.3 pM. The space on the other side sandwiching the through hole was filled with 0.1 × PBS in which the particles were not dispersed.
　イオン電流の測定は、０．１Ｖのｄｃ電圧Ｖｂを印加すること、および、１ＭＨｚのサンプリングレートにて出力電力を記録すること、によって行った。当該測定には、自家製の電流増幅器と、デジタイザー（National Instruments）とを用いた。 The ion current was measured by applying a dc voltage Vb of 0.1 V and recording the output power at a sampling rate of 1 MHz. For the measurement, a home-made current amplifier and a digitizer (National Instruments) were used.
　負に帯電したポリスチレン粒子を貫通孔の中に電気泳動的に引き込むために、バイアスポラリティーを設定した。 バ イ ア ス Bias polarity was set in order to electrophoretically pull negatively charged polystyrene particles into the through-holes.
　＜３．データの解析＞
　貫通孔を最初に流れるイオン電流をゼロとして、イオン電流の変化を観察した。当該観察は、０．５ｓの時間枠内にて、Ｉｉｏｎ－ｔデータからリニアフィット成分を差し引くことによって行った。２００ｐＡよりも大きなイオン電流を抽出した。 <3. Data analysis>
The change in ion current was observed with the ion current flowing first through the through-hole being zero. The observation was performed by subtracting the linear fit component from the I ion -t data within a time frame of 0.5 s. Ion currents greater than 200 pA were extracted.
　＜４．表面電位の評価＞
　０．１×ＰＢＳ中におけるＡｌ２Ｏ３、Ｓｉ３Ｎ４、および、Ａｌ２Ｏ３／Ｓｉ３Ｎ４の有限要素解析を、ポアソン・ボルツマンの理論、および、ネルンスト・プランクの理論にしたがい、ＡＣ／ＤＣモジュール、および、反応工学モジュールを備えたＣＯＭＳＯＬを用いて行った。シミュレーションでは、厚さ５００ｎｍ、半径５００ｎｍである電解質／基材のディスクとして、円筒座標システムを用いた。 <4. Evaluation of surface potential>
The finite element analysis of Al 2 O 3 , Si 3 N 4 , and Al 2 O 3 / Si 3 N 4 in 0.1 × PBS is performed according to Poisson-Boltzmann theory and Nernst-Planck theory, The test was performed using a COMSOL equipped with an AC / DC module and a reaction engineering module. The simulation used a cylindrical coordinate system as an electrolyte / substrate disk with a thickness of 500 nm and a radius of 500 nm.
　厚さがｔＡＬＤであるＡｌ２Ｏ３層を、電解質と基材との境界に挿入した。表面電位分布を、Ａｌ２Ｏ３とＳｉ３Ｎ４との境界にて、可変電荷密度σＡｌ２Ｏ３／Ｓｉ３Ｎ４の下で算出した。Ａｌ２Ｏ３およびＳｉ３Ｎ４の誘電率として、９．０および９．７を用いた。０．１×ＰＢＳバッファー（１３．７ｍＭのＮａＣｌを含む溶液）中におけるＮａ＋およびＣｉ－のモビリティーとして、５．１９×１０－８ｍ２Ｖ－１Ｓ－１、および、７．９１×１０－８ｍ２Ｖ－１Ｓ－１を用いた。 An Al 2 O 3 layer having a thickness of t ALD was inserted at the boundary between the electrolyte and the substrate. The surface potential distribution at the boundary of Al 2 O 3 and Si 3 N 4, was calculated under the variable charge density σ Al2O3 / Si3N4. 9.0 and 9.7 were used as the dielectric constants of Al 2 O 3 and Si 3 N 4 . The mobility of Na + and Ci − in 0.1 × PBS buffer (solution containing 13.7 mM NaCl) was 5.19 × 10 −8 m 2 V −1 S −1 and 7.91 × 10 -8 m 2 V −1 S −1 was used.
　＜５．イオン輸送のシミュレーション＞
　イオン輸送のシミュレーションを、ＡＣ／ＤＣモジュール、反応工学モジュール、および、計算流体力学モジュール（Computational Fluid Dynamics：ＣＦＤ）を備えたＣＯＭＳＯＬを用いて行った。 <5. Simulation of ion transport>
Simulation of ion transport was performed using COMSOL equipped with an AC / DC module, a reaction engineering module, and a Computational Fluid Dynamics (CFD) module.
　固液界面のシミュレーションに加えて、イオン電流に対する電気浸透流の影響を考慮するために、ナビエ・ストークス方程式を用いた。このとき、水の動的粘度ηとして、１０－３Ｐａ・ｓを用いた。 In addition to the simulation of the solid-liquid interface, the Navier-Stokes equation was used to consider the effect of electroosmotic flow on ionic current. At this time, 10 −3 Pa · s was used as the dynamic viscosity η of water.
　ポリスチレン粒子の表面電荷密度、および、貫通孔の壁面の表面電荷密度を、ゼータサイザー（Malvern Panalytical）を用いて測定したゼータ電位にしたがって算出した。 (4) The surface charge density of the polystyrene particles and the surface charge density of the wall surface of the through-hole were calculated according to the zeta potential measured using a Zetasizer (Malvern @ Panalytical).
　バルクの特性（例えば、誘電率、および、伝導率）は、水、Ｓｉ３Ｎ４、および、Ａｌ２Ｏ３の特性とした。 The properties of the bulk (for example, dielectric constant and conductivity) were those of water, Si 3 N 4 , and Al 2 O 3 .
　＜６．試験結果１＞
　厚さｔｍが５０ｎｍであるＳｉ３Ｎ４膜中に形成した、直径ｄｐｏｒｅが１．２μｍである貫通孔であって、厚さＴＡＬＤが様々であるＡｌ２Ｏ３層によって覆われた貫通孔を流れるイオン電流Ｉｉｏｎを、０．１×ＰＢＳ（Merck Millipore）を用い、ｄｃ電圧Ｖｂを±０．５Ｖの範囲内として、測定した。その結果を図４の４０１に示す。 <6. Test result 1>
The thickness t m was formed on the Si 3 N 4 film in a 50 nm, the diameter d pore is a through-hole is 1.2 [mu] m, was covered by the Al 2 O 3 layer with varying thickness T ALD The ion current I ion flowing through the through-hole was measured using 0.1 × PBS (Merck Millipore) with the dc voltage Vb within the range of ± 0.5 V. The result is shown at 401 in FIG.
　貫通孔のコンダクタンスＧｏｐｅｎは、１８０±１４ｎＳであった。Ａｌ２Ｏ３層によって覆われた貫通孔は、Ａｌ２Ｏ３層によって覆われていない貫通孔と同様のコンダクタンスＧｏｐｅｎを示した。直径ｄｐｏｒｅ、および、厚さｔｍと比較して、Ａｌ２Ｏ３層の厚さＴＡＬＤが小さいため、同様のコンダクタンスＧｏｐｅｎを示したと考えられる。 The conductance G open of the through hole was 180 ± 14 nS. Holes covered by the Al 2 O 3 layer showed similar conductance G open a through hole that is not covered by the Al 2 O 3 layer. Since the thickness T ALD of the Al 2 O 3 layer is smaller than the diameter d pore and the thickness t m , it is considered that the same conductance G open was exhibited.
　Ｉｉｏｎ－Ｖｂ特性に対するＡｌ２Ｏ３層の影響は小さかったものの、ζ電位の測定結果は、表面電荷状態に対してＡｌ２Ｏ３層が影響することを示している。ゼータサイザー（Malvern Panalytical）を用いて、表面のζ電位であるζｓを測定した。ζ電位によって、Ａｌ２Ｏ３／Ｓｉ３Ｎ４の表面近傍における電気浸透を評価することができる。 Although the influence of the Al 2 O 3 layer with respect to I ion -V b properties was small, the measurement result of ζ potential shows that the Al 2 O 3 layer is affected to the surface charge state. With Zetasizer (Malvern Panalytical), it was measured zeta s a zeta potential of the surface. The electro-osmosis near the surface of Al 2 O 3 / Si 3 N 4 can be evaluated by the ζ potential.
　ζ電位であるζｓの測定結果を図４の４０２に示す。図４の４０２に示すように、ＴＡＬＤが０から１へ減少する間、ζｓの値は急激に減少し、ＴＡＬＤが１から６へ増加する間、ζｓの値は増加した。また、ＴＡＬＤが６よりも大きい場合には、ζｓの値は略一定であった。 The measurement results of a zeta potential zeta s shown in 402 of FIG. As shown in 402 of FIG. 4, while the T ALD decreases from 0 to 1, the value of the zeta s decreases sharply, while the T ALD increases from 1 to 6, the value of the zeta s increased. Also, if T ALD is greater than 6, the value of zeta s was nearly constant.
　図４の４０３に、上述した実施例から示唆される、貫通孔の壁面近傍の状態を示す。当該状態では、実験的に得られたζｓの値から考えて、Ｓｉ３Ｎ４、および、Ａｌ２Ｏ３を、各々、σＳｉ３Ｎ４＝－２５ｍＣ／ｍ２、および、σＡｌ２Ｏ３＝－１５ｍＣ／ｍ２の負の表面電荷を有する層としてモデル化することができる。図４の４０４より、（ｉ）Ａｌ２Ｏ３原子層は水分子を透過させ、その結果、原子層成膜後においてもＳｉ３Ｎ４表面上には表面電荷が生成されること、および、（ｉｉ）水分子の透過距離は有限であることから、原子層の厚さによって、Ｓｉ３Ｎ４／Ａｌ２Ｏ３界面における電荷密度、ひいては有効表面電位が制御できること、が判った。 403 of FIG. 4 shows a state near the wall surface of the through-hole, which is suggested from the above-described embodiment. In this state, given the value of the experimentally obtained ζ s, Si 3 N 4, and the Al 2 O 3, respectively, σ Si3N4 = -25mC / m 2 , and, σ Al2O3 = -15mC / it can be modeled as a layer having a negative surface charge of m 2. From 404 in FIG. 4, (i) the Al 2 O 3 atomic layer allows water molecules to permeate, and as a result, a surface charge is generated on the Si 3 N 4 surface even after the atomic layer is formed, and (Ii) Since the transmission distance of water molecules is finite, it has been found that the charge density at the Si 3 N 4 / Al 2 O 3 interface, and consequently the effective surface potential, can be controlled by the thickness of the atomic layer.
　図４の４０１～４０４から、０．６ｍＶの分解能にて表面電位を制御できることが明らかになった。 ４０１ From 401 to 404 in FIG. 4, it was revealed that the surface potential can be controlled with a resolution of 0.6 mV.
　＜７．試験結果２＞
　本実施例では、貫通孔を通過する粒子を検出した。 <7. Test result 2>
In this example, particles passing through the through-hole were detected.
　試験モデルとして、直径が０．７８μｍである、カルボン酸塩化されたポリスチレン粒子を用いた。単一粒子の検出は、Ｖｂ＝＋０．１Ｖにおいて貫通孔を流れるＩｉｏｎを測定することによって行った。 As test model, carboxylated polystyrene particles having a diameter of 0.78 μm were used. Single particles were detected by measuring I ion flowing through the through hole at V b = + 0.1V.
　図５の５０１に、ＴＡＬＤが４ｎｍである場合のＩｉｏｎを示す。一方、ＴＡＬＤが１０ｎｍよりも厚い場合には、粒子は、貫通孔を通過することができず、貫通孔の内部に捕捉された。これは、粒子と、正に帯電したＡｌ２Ｏ３層の表面との間にはたらく、強いクーロン引力が原因であると考えられる。 Reference numeral 501 in FIG. 5 shows the I ion when T ALD is 4 nm. On the other hand, when T ALD was thicker than 10 nm, the particles could not pass through the through-hole and were trapped inside the through-hole. This is believed to act between the particles and the positively charged the Al 2 O 3 layer surface, is caused strong Coulomb attractive force is.
　図５の５０２に示すように、粒子の速度は、各粒子が貫通孔を通過するために要した時間を示すイオンスパイク幅ｔｄから推定される。図５の５０３は、ｔｄとｔＡＬＤとの相関関係を示している。ｔＡＬＤが１．５ｎｍであるときに、ｔｄは大きくなり、ｔＡＬＤが１．５ｎｍよりも大きくなるにしたがって、ｔｄは小さくなった。このことは、ｔＡＬＤが大きくなるにしたがって、ｔｄが小さくなる（換言すれば、粒子の速度が増す）ことを示している。 As shown in 502 of FIG. 5, the speed of the particles, each particle is estimated from the ion spike width t d that indicates the time taken to pass through the through hole. Reference numeral 503 in FIG. 5 shows a correlation between t d and t ALD . When t ALD was 1.5 nm, t d increased, and as t ALD became greater than 1.5 nm, t d decreased. This indicates that td decreases as t ALD increases (in other words, the velocity of the particles increases).
　図５の５０４に、貫通孔内を流れる電気浸透流を示す。図４の４０２に示すように、ＴＡＬＤの値に応じてζｓの値は変化する。この時、ＴＡＬＤの値の絶対値に比例して、電気浸透流の速度は変化する。粒子の速度は、粒子に作用する電気泳動の力と、粒子に作用する電気浸透流の力とによって決まる。それ故に、電気浸透流の速度が変化すると、粒子の速度も変化する。図５の５０５に、本試験にて測定された粒子の速度、および、電気浸透流を考慮した理論上の粒子の速度を示す。図５の５０５から、本試験にて測定された粒子の速度と、電気浸透流を考慮した理論上の粒子の速度とが、一致することが判った。 An electroosmotic flow flowing in the through hole is shown at 504 in FIG. As shown in 402 of FIG. 4, the value of zeta s depending on the value of T ALD changes. At this time, the speed of the electroosmotic flow changes in proportion to the absolute value of the value of T ALD . The speed of the particles is determined by the electrophoretic force acting on the particles and the electroosmotic force acting on the particles. Therefore, as the speed of the electroosmotic flow changes, so does the speed of the particles. In FIG. 5, reference numeral 505 shows the particle velocity measured in this test and the theoretical particle velocity in consideration of the electroosmotic flow. From 505 in FIG. 5, it was found that the particle velocity measured in the present test and the theoretical particle velocity in consideration of the electroosmotic flow coincide.
　＜８．試験結果３＞
　図５の５０２に示すＩｉｏｎ－ｔのデータから、粒子の捕捉率ｆ（＝１／Δｔ）を算出した。なお、Δｔとは、２つの連続したパルス間の時間を意図する。図６の６０１に示すように、ｆは、ＴＡＬＤに応じて著しく変化した。 <8. Test result 3>
The particle capture rate f (= 1 / Δt) was calculated from the data of I ion −t indicated by 502 in FIG. Note that Δt means the time between two consecutive pulses. As shown at 601 in FIG. 6, f changed significantly according to T ALD .
　図６の６０２に、軸方向へ向かう電気泳動の速度（ＶＥＰ）と、電気浸透流の速度（ＶＥＯＦ）との有限要素解析の結果を示す。図６の６０２において、「Ｚ」は、貫通孔の中央からの軸方向への距離を示し、「ｒ」は、半径方向の位置を示している。図６の６０２に示すように、ＶＥＰの値は、ＶＥＯＦの値よりも大きかった。 6 shows the result of finite element analysis of the speed of electrophoresis (V EP ) in the axial direction and the speed of electroosmotic flow (V EOF ). In 602 of FIG. 6, “Z” indicates a distance in the axial direction from the center of the through hole, and “r” indicates a position in the radial direction. So it is shown in 602 in FIG values of V EP may larger than the values of V EOF.
　本発明は、微細な流路を用いる技術に広く利用することができる。本発明は、例えば、物質を検出する分野、物質を同定する分野、および、物質を移動させる分野に用いることができる。 The present invention can be widely used for technology using a fine channel. The present invention can be used, for example, in the fields of detecting a substance, identifying a substance, and moving a substance.
　　１　流路
　　２　負極
　　３　正極
　　４　電流計
　１０　基材
　２０　被膜層 DESCRIPTION OF SYMBOLS 1 Flow path 2 Negative electrode 3 Positive electrode 4 Ammeter 10 Substrate 20 Coating layer

Claims (12)

  1. 　物質が移動する経路である貫通孔が設けられている基材と、
    　上記貫通孔の壁面上に設けられている、原子層を含んでいる被膜層と、を備えていることを特徴とする、流路。     A substrate provided with a through-hole that is a path through which a substance moves,
    And a coating layer including an atomic layer provided on a wall surface of the through hole.
  2. 　上記被膜層の厚さは、上記原子層の厚さの２００倍以下であることを特徴とする、請求項１に記載の流路。 The flow path according to claim 1, wherein the thickness of the coating layer is 200 times or less the thickness of the atomic layer.
  3. 　上記原子層は、Ａｌ２Ｏ３、ＨｆＯ２、ＴｉＯ２、ＺｎＯ、または、ＳｉＯ２の原子層であることを特徴とする、請求項１または２に記載の流路。 The flow path according to claim 1, wherein the atomic layer is an atomic layer of Al 2 O 3 , HfO 2 , TiO 2 , ZnO, or SiO 2 .
  4. 　請求項１～３の何れか１項に記載の流路と、
    　上記貫通孔を挟むように配置されている電極対と、を備えていることを特徴とする電極構造体。     A flow channel according to any one of claims 1 to 3,
    An electrode structure comprising: an electrode pair disposed so as to sandwich the through hole.
  5. 　基材に設けられている、物質が移動する経路である貫通孔の壁面上に、原子層を含んでいる被膜層を形成する被膜層形成工程を有していることを特徴とする、流路の製造方法。 A flow path, comprising a coating layer forming step of forming a coating layer containing an atomic layer on a wall surface of a through hole provided on a base material, which is a path through which a substance moves. Manufacturing method.
  6. 　上記被膜層形成工程では、上記原子層の厚さの２００倍以下の厚さになるように上記被膜層が形成されることを特徴とする、請求項５に記載の流路の製造方法。 The method according to claim 5, wherein, in the coating layer forming step, the coating layer is formed so as to have a thickness of 200 times or less the thickness of the atomic layer.
  7. 　上記原子層は、Ａｌ２Ｏ３、ＨｆＯ２、ＴｉＯ２、ＺｎＯ、または、ＳｉＯ２の原子層であることを特徴とする、請求項５または６に記載の流路の製造方法。 The method according to claim 5, wherein the atomic layer is an atomic layer of Al 2 O 3 , HfO 2 , TiO 2 , ZnO, or SiO 2 .
  8. 　上記被膜層形成工程では、原子層堆積法によって上記原子層を形成することを特徴とする、請求項５～７の何れか１項に記載の流路の製造方法。 The method according to any one of claims 5 to 7, wherein in the coating layer forming step, the atomic layer is formed by an atomic layer deposition method.
  9. 　基材に設けられている、物質が移動する経路である貫通孔の壁面上に、原子層を含んでいる被膜層を形成する被膜層形成工程と、
    　上記貫通孔を挟むように電極対を設ける電極対形成工程と、を有することを特徴とする、電極構造体の製造方法。     A coating layer forming step of forming a coating layer containing an atomic layer on a wall surface of a through-hole that is provided on a base material and is a path through which a substance moves,
    An electrode pair forming step of providing an electrode pair so as to sandwich the through hole.
  10. 　上記被膜層形成工程では、上記原子層の厚さの２００倍以下の厚さになるように上記被膜層が形成されることを特徴とする、請求項９に記載の電極構造体の製造方法。 The method according to claim 9, wherein, in the coating layer forming step, the coating layer is formed to have a thickness of 200 times or less the thickness of the atomic layer.
  11. 　上記原子層は、Ａｌ２Ｏ３、ＨｆＯ２、ＴｉＯ２、ＺｎＯ、または、ＳｉＯ２の原子層であることを特徴とする、請求項９または１０に記載の電極構造体の製造方法。 The method according to claim 9, wherein the atomic layer is an atomic layer of Al 2 O 3 , HfO 2 , TiO 2 , ZnO, or SiO 2 .
  12. 　上記被膜層形成工程では、原子層堆積法によって上記原子層を形成することを特徴とする、請求項９～１１の何れか１項に記載の電極構造体の製造方法。 The method of manufacturing an electrode structure according to any one of claims 9 to 11, wherein, in the coating layer forming step, the atomic layer is formed by an atomic layer deposition method.
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