Electroosmotic flow pump

Abstract

To provide an electroosmotic flow pump capable of efficiently performing discharge and suction.SOLUTION: The first transporter 11 includes a first channel 11a in which positive charges are fixed, a first opening 11a communicating with the first channel 11b, and a first electrode 11a disposed at a position away from the first opening 11b of the first channel 11c. The second transporter 12 has a second channel 12a in which negative charges are fixed, a second opening 12a communicating with the second channel 12b, and a second electrode 12a disposed at a position away from the second opening 12b of the second channel 12c. A current / voltage application means 14 is provided so as to apply a current or a voltage between the first and second electrodes 11c and 12c. When a current or a voltage is applied between the 11c of the first electrodes and the 12c of the second electrodes by a current / voltage application means 14, an ion current flows through the fluid in the first flow path 11a and the second flow path 12a, and an electroosmotic flow is generated in each fluid.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an electroosmotic pump. [Background technology]

[0002] In the field of biomedicine, localized ejection and suction of solutions into living organisms has been widely used in the past, such as drug administration from skin patches or implanted devices, molecule administration to cultured cells or tissues, and sampling and analysis of body fluids. For example, when ejecting a drug solution from a brain probe, the most common method is the so-called "pressure-based" method, in which hydraulic pressure generated by a mechanical pump such as a syringe pump or an electroosmotic flow pump is transmitted to eject the solution (see, for example, Non-Patent Documents 1 and 2).

[0003] However, this "pressure-based" method has the problem that it is extremely difficult to control the discharge volume because pressure is not easily transmitted to localized areas of the microdevice. Therefore, pump systems that directly utilize electrophoresis or electroosmotic flow have been developed to provide high control over the discharge and suction volumes (see, for example, Non-Patent Document 3).

[0004] In electrophoretic pumping systems, charged particles or molecules themselves migrate through an electrolyte, rather than through a liquid flow. Therefore, the efficiency of relatively large substances such as dopamine is low, and neutral substances with no charge do not move. In contrast, electroosmotic flow is a liquid flow in an ionic conductor generated by passing an electric current through a solid ionic conductor. As shown in Figure 9, this flow occurs when there is a large difference in the mobility of cations and anions in the liquid due to factors such as the presence of fixed charges in the ionic conductor (see, for example, Non-Patent Documents 4 and 5). Therefore, even relatively large or neutral substances can be moved more easily than with electrophoresis.

[0005] Pump systems that utilize electroosmotic flow have been used mainly for capillary electrophoresis and liquid transport in microchannels. This pump system utilizes the fact that the inner walls of narrow channels have glass silanol groups (negative charges), and the movement of cations, which have relatively high mobility, generates a flow of hydrated water, i.e., an electroosmotic flow.

[0006] In addition to capillaries, electroosmotic flow occurs using the same principle when a hydrogel with a fixed charge or a porous body has a fixed charge on the pore wall, and devices utilizing this have also been developed. For example, the present inventors have developed contact lenses that can pump up tears using electroosmotic flow, such as contact lenses made of hydrogels with a fixed charge (see, for example, Non-Patent Document 6 or Patent Document 1), and porous microneedles with a fixed charge on the pore wall to deliver drugs or vaccines under the skin using electroosmotic flow (see, for example, Non-Patent Document 7 or Patent Document 2). [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] R. Chen, A. Canales, P. Anikeeva, “Neural recording and modulation technologies”, Nature Reviews Materials, 2017, 2, 16093 [Non-patent document 2] SS Kare, CM Rountree, JB Troy, JD Finan and L. Saggere, “Neuromodulation using electroosmosis”, J. Neural Eng., 2021, 18, 04602 [Non-patent document 3] L. Waldherr et al., “Targeted chemotherapy of glioblastoma spheroids with an iontronic pump”, Adv. Mater. Technol., 2021, 6, 2001302 [Non-patent document 4] MJ Pikal, “The role of electroosmotic flow in transdermal iontophoresis”, Adv. Drug Deliv. Rev., 2001, 46, 281 [Non-patent document 5] BJ Kirby, EF Hasselbrink, “Zeta potential of microfluidic substrates: 1. Theory, experimental techniques, and effects on separations”, Electrophoresis, 2004, 25, 187 [Non-patent document 6] S. Kusama, S. Yoshida, K. Sato, M. Nishizawa, “Self-moisturizing smart contact lens employing electroosmosis”, Adv. Mater. Technol., 2020, 5, 1900889 [Non-Patent Document 7] S. Kusama et al., “Transdermal electroosmotic flow generated by a porous microneedle array patch”, Nat. Commun., 2021, 12, 658 [Patent documents]

[0008] [Patent Document 1] International Publication No. WO2017 / 178964 [Patent Document 2] International Publication No. WO2020 / 179850 Summary of the Invention [Problem to be solved by the invention]

[0009] Conventional pump systems that utilize electroosmotic flow, such as capillaries, microchannels, and the contact lenses and porous microneedles described in Non-Patent Documents 6 and 7 and Patent Documents 1 and 2, offer excellent control over the amount of discharge and suction. However, these systems only utilize the movement of either positive ions (cations) or negative ions (anions), and there is a constant demand for systems that can discharge and suction more efficiently.

[0010] The present invention has been made in view of the above-mentioned problems, and has as its object to provide an electroosmotic pump that can perform discharge and suction efficiently. [Means for solving the problem]

[0011] In order to achieve the above object, the electroosmotic flow pump of the present invention comprises a first transporter having a first flow path in which a positive charge is fixed, a first opening communicating with the first flow path, and a first electrode arranged at a position away from the first opening of the first flow path; a second transporter having a second flow path in which a negative charge is fixed, a second opening communicating with the second flow path, and a second electrode arranged at a position away from the second opening of the second flow path; and current / voltage application means provided so as to be able to apply a current or voltage between the first electrode and the second electrode, wherein when a current or voltage is applied between the first electrode and the second electrode by the current / voltage application means, an ionic current flows in the fluid in the first flow path and the fluid in the second flow path, thereby generating an electroosmotic flow in each fluid.

[0012] The electroosmotic pump according to the present invention is used as follows: First, fluids are introduced into the first and second flow paths. At this time, a positive charge is fixed in the first flow path, and a negative charge is fixed in the second flow path. In this state, a current or voltage is applied between the first and second electrodes by the current / voltage application means, and an ionic current is passed through the fluid in the first flow path and the fluid in the second flow path, thereby generating an electroosmotic flow in each fluid.

[0013] For example, by applying a current or voltage using the current / voltage application means to cause an ionic current to flow from the second electrode to the first electrode, an electroosmotic flow can be generated in which the fluid in the first flow path flows outward from the first opening, and an electroosmotic flow in which the fluid in the second flow path flows outward from the second opening. This allows the fluid in the first flow path and the fluid in the second flow path to be ejected. Furthermore, by applying a current or voltage using the current / voltage application means to cause an ionic current to flow from the first electrode to the second electrode, an electroosmotic flow can be generated in which the fluid in the first flow path flows inward from the first opening, and an electroosmotic flow in which the fluid in the second flow path flows inward from the second opening. This allows the external fluid to be sucked through the first opening and the second opening. Thus, the electroosmotic pump according to the present invention can simultaneously suck or eject fluid from both the first transporter and the second transporter, providing more efficient sucking and ejecting than pumps that only suck or eject fluid from one of them.

[0014] The electroosmotic flow pump according to the present invention can control the flow rate of the generated electroosmotic flow by adjusting the current or voltage applied by the current / voltage application means, thereby providing excellent control over the discharge and suction rates. The electroosmotic flow pump according to the present invention can be used for administering drugs and sampling body fluids from living organisms, but can also be used for other applications involving the discharge or suction of fluids. For example, when used for administering drugs, a fluid containing the drug to be administered can be used as the fluid to be placed in the first flow path and / or the second flow path.

[0015] In the electroosmotic pump of the present invention, the first transporter may be made of any material capable of fixing a positive charge in the first flow path, and the second transporter may be made of any material capable of fixing a negative charge in the second flow path. The first and second transporters may be made of, for example, a hydrogel material, a porous resin, an oxide, a metal, or a biodegradable material.

[0016] In the electroosmotic pump according to the present invention, the first transporter may have a higher mobility for anions than for cations when a fluid is introduced into the first flow path, and may, for example, have positive charges immobilized on the wall surface of the first flow path, have positive charges embedded in the surface layer, or be made of a hydrogel containing positively charged functional groups. The second transporter may have a higher mobility for cations than for anions when a fluid is introduced into the second flow path, and may, for example, have negative charges immobilized on the wall surface of the second flow path, have negative charges embedded in the surface layer, or be made of a hydrogel containing negatively charged functional groups.

[0017] In the electroosmotic pump according to the present invention, the fluid in the first flow path and the fluid in the second flow path may be any fluid that ionizes into cations and anions in each flow path, and is preferably an electrolyte solution, for example. The fluid in the first flow path and the fluid in the second flow path may be the same type or different types. Furthermore, the first transporter and the second transporter may be arranged such that the first opening and the second opening are adjacent to each other, or may be arranged such that the first opening and the second opening are spaced apart.

[0018] The electroosmotic pump according to the present invention may include a storage chamber configured to store a predetermined fluid and communicate with the first and second openings, the storage chamber having a third opening at a location other than the locations communicating with the first and second openings, and configured such that, when a current or voltage is applied by the current / voltage application means, an ionic current flows through the fluid in the first flow path, the predetermined fluid stored in the storage chamber, and the fluid in the second flow path, thereby generating an electroosmotic flow in the fluid in the first flow path and the fluid in the second flow path. In this case, discharge and suction can be performed through the third opening. Furthermore, because the ionic current passes through the first flow path, the storage chamber, and the second flow path and does not leak to the outside, the ionic current can be prevented from affecting external biological cells, etc.

[0019] In the electroosmotic pump according to the present invention, the first transporter may be elongated, the first opening may be formed at one end, and the first electrode may be provided at the other end. The second transporter may be elongated, the second flow path may be insulated from the first flow path, and the second opening may be formed at one end adjacent to the first opening, and the second electrode may be provided at the other end. In this case, the electroosmotic pump has an elongated tubular shape, and discharge or suction can be performed from one end on the distal side while adjusting the current or voltage at the other end on the proximal side. Therefore, for example, the pump may be inserted into a channel of an endoscope and used for discharging a drug into the body or sampling a body fluid.

[0020] In the electroosmotic pump according to the present invention, the first transporter and the second transporter are each thin membrane-like and are stacked on top of each other in the thickness direction to form a sheet-like body with the first flow path and the second flow path insulated from each other. The sheet-like body may have one or more communication holes formed on one surface along the thickness direction so as to communicate with the first flow path and the second flow path without penetrating to the other surface, the storage chamber may be formed from the communication hole, and the third opening may be an opening of the communication hole formed on the one surface of the sheet-like body. In this case, discharge and suction can be performed through the third opening on one surface of the sheet-like body. Therefore, for example, by forming multiple third openings on one surface of the sheet-like body and attaching the sheet-like body to the skin so that the one surface is in contact with the skin, discharge and suction can be performed over a relatively wide area of ​​the skin's surface.

[0021] The electroosmotic flow pump according to the present invention may be configured such that the first transporter and the second transporter can be attached to the biological tissue so that the first opening and the second opening are in contact with the biological tissue. When the first transporter and the second transporter are attached to the biological tissue and a current or voltage is applied by the current / voltage application means, an ionic current flows through the fluid in the first flow path, the fluid inside the biological tissue, and the fluid in the second flow path, thereby generating an electroosmotic flow in the fluid in the first flow path and the fluid in the second flow path. In this case, the first transporter and the second transporter can be disposed at any positions separated from each other. The first transporter and the second transporter may each be one or more. Furthermore, by attaching the first transporter and the second transporter to the adhesive surface of an adhesive sheet so that the first opening and the second opening are on the opposite side of the adhesive surface, the patch can be easily used by simply attaching the adhesive sheet to biological tissue such as skin. The first transporter and the second transporter may be attached to separate adhesive sheets.

[0022] The kit for applying biological tissue according to the present invention is a kit for applying biological tissue to prepare a patch for application to biological tissue to be applied to biological tissue, and includes a first transporter having a first flow path in which a positive charge is fixed, a first opening communicating with the first flow path, and a first electrode arranged at a position away from the first opening of the first flow path, a second transporter having a second flow path in which a negative charge is fixed, a second opening communicating with the second flow path, and a second electrode arranged at a position away from the second opening of the second flow path, and a voltage applying device capable of applying a current or a voltage between the first electrode and the second electrode. and a current / voltage application means provided in the first flow path, wherein the first transporter and the second transporter are configured to be affixed to the biological tissue so that the first opening and the second opening come into contact with the biological tissue, and wherein when the first transporter and the second transporter are affixed to the biological tissue and a current or voltage is applied by the current / voltage application means, an ionic current flows through the fluid in the first flow path, the fluid inside the biological tissue, and the fluid in the second flow path, and an electroosmotic flow is generated in the fluid in the first flow path and the fluid in the second flow path.

[0023] The kit for application to biological tissue according to the present invention can be suitably used to prepare a patch for application to biological tissue comprising the electroosmotic pump according to the present invention. The kit for application to biological tissue according to the present invention can be easily used by, for example, attaching the first transporter and the second transporter to the adhesive surface of an adhesive sheet so that the first opening and the second opening are on the opposite side of the adhesive surface, and then simply attaching the adhesive sheet to the biological tissue. The first transporter and the second transporter may also be attached to separate adhesive sheets.

[0024] The biological tissue patch prepared using the biological tissue patch kit of the present invention can simultaneously eject or aspirate both the first transporter and the second transporter, allowing for more efficient ejection or aspirate than patches that eject or aspirate only one of them. Furthermore, the biological tissue patch can control the flow rate of the generated electroosmotic flow by adjusting the current or voltage applied by the current / voltage application means, providing excellent control over the ejection and aspirate amounts. The biological tissue patch can be used, for example, to administer drugs to biological tissue or sample body fluids from biological tissue. [Effects of the Invention]

[0025] According to the present invention, it is possible to provide an electroosmotic pump that can perform discharge and suction efficiently. [Brief explanation of the drawings]

[0026] [Figure 1] 1A and 1B are a perspective view and a cross-sectional view, respectively, showing an electroosmotic pump according to a first embodiment of the present invention; [Figure 2] 1A and 1B are a perspective view and a cross-sectional view, respectively, showing an electroosmotic pump according to a second embodiment of the present invention. [Figure 3] 10A and 10B are a perspective view and a cross-sectional view, respectively, showing an electroosmotic pump according to a third embodiment of the present invention in use; [Figure 4] FIG. 1 is a cross-sectional view showing a test method using a Franz cell with a horizontal capillary for an electroosmotic flow generation test for each sample constituting a first transporter and a second transporter in the electroosmotic flow pumps of the first to third embodiments of the present invention. [Figure 5]Figure 4 shows the results of the electroosmotic flow generation test, including (a) a graph showing the change over time in the cumulative amount of water transported by electroosmotic flow in a negatively charged hydrogel and a positively charged hydrogel, (b) a graph showing the relationship between the flow rate of electroosmotic flow and the current value in a porous elastomer filled with a negatively charged hydrogel and a positively charged hydrogel, and (c) a graph showing the relationship between the flow rate of electroosmotic flow and the current value in a PAMPS-modified porous resin (negatively charged) and an unmodified porous resin. [Figure 6] FIG. 1 shows a water transport test by electroosmosis of an electroosmotic flow pump according to a first embodiment of the present invention. (a) Cross-sectional views of the tip of the tube constituting the first transporter and the second transporter, with the tip cut out, a cross-sectional view of the two tubes integrated to form a storage section, and a cross-sectional view of the electroosmotic flow pump used in the test. (b) Cross-sectional views of five types of electroosmotic flow pumps used in the test, which combine a positively charged hydrogel (A in the figure), a negatively charged hydrogel (C in the figure), and a neutral gel (N in the figure) as the first transporter and the second transporter. (c) Side views showing the observation results of water movement in a glass capillary from 0 to 3 minutes after applying a current of 3 mA and −3 mA to the AC-type electroosmotic flow pump shown in (b). (d) A graph showing the mobility (flow rate) of the electroosmotic flow when a current of 3 mA is applied to the five types of electroosmotic flow pumps shown in (b). [Figure 7] FIG. 6(b) is a graph showing the change in the amount of transported substance (integrated) of Rhodamine B over time when a current of 3 mA was applied and when no current was applied, in a discharge performance (controllability) evaluation test of the AC-type electroosmotic pump shown in FIG. 6(b). FIG. 6(a) is a graph showing the change in the amount of transported substance (integrated) of Rhodamine B over time when a current of 3 mA was applied and when no current was applied. FIG. 6(b) is a graph showing the change in the substance transport efficiency over time calculated from the results of FIG. 6(a) and FIG. 6(d). [Figure 8] FIG. 10 shows, for an electroosmotic pump according to a third embodiment of the present invention, (a) a cross-sectional view illustrating a discharge test method; (b) a fluorescent microscope photograph of the boundary between the gel and each porous elastomer when no current is applied; (c) a fluorescent microscope photograph of the boundary between the gel and the first transporter when a current of 1 mA is applied; and (d) a fluorescent microscope photograph of the boundary between the gel and the second transporter when a current of 1 mA is applied. [Figure 9] FIG. 1 is an explanatory diagram showing the principle of how electroosmotic flow occurs in a conventional ionic conductor having a fixed charge. DETAILED DESCRIPTION OF THE INVENTION

[0027] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. FIG. 1 shows an electroosmotic pump according to a first embodiment of the present invention. As shown in FIGS. 1(a) and 1(b), electroosmotic pump 10 is tubular and includes first transporter 11, second transporter 12, storage chamber 13, and current / voltage application means 14.

[0028] The first transporter 11 is made of a flexible, elongated tube. The first transporter 11 has a first flow path 11a extending from one end to the other end, a first opening 11b formed at one end and communicating with the first flow path 11a, and a first electrode 11c provided at the other end of the first flow path 11a. The first flow path 11a has a fixed positive charge.

[0029] The second transporter 12 is made of a thin, flexible tube. The second transporter 12 has a second flow path 12a extending from one end to the other end, a second opening 12b formed at one end and communicating with the second flow path 12a, and a second electrode 12c provided at the other end of the second flow path 12a. The second flow path 12a has a fixed negative charge. The second transporter 12 is provided along the first transporter 11 so that the second opening 12b is adjacent to the first opening 11b and the second flow path 12a is insulated from the first flow path 11a.

[0030] The first transporter 11 may be made of any material capable of fixing a positive charge in the first flow path 11a, and the second transporter 12 may be made of any material capable of fixing a negative charge in the second flow path 12a. The first transporter 11 and the second transporter 12 may be made of, for example, a hydrogel material, a porous resin, an oxide, a metal, or a biodegradable material.

[0031] Here, the hydrogel material is a material that forms a hydrogel when dispersed in water (a dispersion medium). Examples of hydrogel materials include agar, gelatin, agarose, xanthan gum, gellan gum, sclerotium gum, gum arabic, gum tragacanth, karaya gum, cellulose gum, tamarind gum, guar gum, locust bean gum, glucomannan, chitosan, carrageenan, quince seed, galactan, mannan, starch, dextrin, curdlan, casein, pectin, collagen, fibrin, peptides, chondroitin sulfates such as sodium chondroitin sulfate, hyaluronic acid (mucopolysaccharides), and hyaluronic acid. Natural polymers such as hyaluronates such as sodium aluronate, alginate salts such as alginic acid, sodium alginate, and calcium alginate, and derivatives thereof; cellulose derivatives such as methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and carboxymethylcellulose, and salts thereof; poly(meth)acrylic acids such as polyacrylic acid, polymethacrylic acid, and acrylic acid-alkyl methacrylate copolymers, and salts thereof;Examples of suitable polymers include polyvinyl alcohol, polyethylene glycol di(meth)acrylate polymers (PPEGDA, PPEGDM), homopolymers or copolymers containing structural units derived from hydroxyethyl methacrylate such as polyhydroxyethyl methacrylate, polyacrylamide, poly(N-isopropylacrylamide), poly2-acrylamido-2-methylpropanesulfonic acid, poly(N-isopropylacrylamide), homopolymers or copolymers containing structural units derived from dimethylacrylamide, homopolymers or copolymers containing structural units derived from vinylpyrrolidone, copolymers containing structural units derived from dimethylacrylamide, polystyrene sulfonic acid, polyethylene glycol, carboxyvinyl polymers, alkyl-modified carboxyvinyl polymers, maleic anhydride copolymers, polyalkylene oxide resins, crosslinked polymers of poly(methyl vinyl ether-alt-maleic anhydride) and polyethylene glycol, crosslinked polyethylene glycol, N-vinylacetamide crosslinked polymers, acrylamide crosslinked polymers, and crosslinked polymers of starch-acrylate graft copolymers; silicones; interpenetrating network hydrogels and semi-interpenetrating network hydrogels (DN hydrogels); and mixtures of two or more of these. ;

[0032] Furthermore, the hydrogel material may contain a monomer unit having ethylenically unsaturated groups at both ends, which are polymerizable groups, so that the resulting polymer has a crosslinked polymer structure and excellent physical strength. The monomer having ethylenically unsaturated groups at both ends may be a monomer to which a structure derived from a hydrophilic polymer is added. Examples of structures derived from hydrophilic polymers include polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, poly(meth)acrylic acid, poly(meth)acrylate, poly(2-hydroxyethyl(meth)acrylate), polytetrahydrofuran, polyoxetane, polyoxazoline, polydimethylacrylamide, polydiethylacrylamide, and poly(2-methacryloyloxyethylphosphorylcholine).

[0033] The hydrogel material may also contain a hydrophilic monomer unit, such as (meth)acrylamide; hydroxyalkyl (meth)acrylates such as 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, and hydroxybutyl (meth)acrylate; (alkyl)aminoalkyl (meth)acrylates such as 2-dimethylaminoethyl (meth)acrylate and 2-butylaminoethyl (meth)acrylate; alkylene glycol mono(meth)acrylates such as ethylene glycol mono(meth)acrylate and propylene glycol mono(meth)acrylate; polyethylene glycol mono(meth)acrylate; Polyalkylene glycol mono(meth)acrylates such as ethylene glycol mono(meth)acrylate and polypropylene glycol mono(meth)acrylate; ethylene glycol allyl ether; ethylene glycol vinyl ether; (meth)acrylic acid; aminostyrene; hydroxystyrene; vinyl acetate; glycidyl (meth)acrylate; allyl glycidyl ether; vinyl propionate; N,N-dimethylmethacrylamide, N,N-diethylmethacrylamide, N-(2-hydroxyethyl)methacrylamide, N-isopropylmethacrylamide, methacryloylmorpholine;N-vinyl-2-pyrrolidone, N-vinyl-3-methyl-2-pyrrolidone, N-vinyl-4-methyl-2-pyrrolidone, N-vinyl-5-methyl-2-pyrrolidone, N-vinyl-6-methyl-2-pyrrolidone, N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone, N-vinyl-5,5-dimethyl-2-pyrrolidone, N-vinyl-3,3,5-trimethyl-2-pyrrolidone, N-vinyl-2-piperidone, N-vinyl-3-methyl-2-piperidone, N-vinyl-4-methyl-2-piperidone, N-vinyl-5-methyl-2-piperidone, N-vinyl-6-methyl-2-piperidone, N-vinyl-6-ethyl-2-piperidone, N-vinyl-3,5-dimethyl-2-piperidone, N-vinyl-4,4 N-vinyl lactams such as N-dimethyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-caprolactam, N-vinyl-4-methyl-2-caprolactam, N-vinyl-7-methyl-2-caprolactam, N-vinyl-7-ethyl-2-caprolactam, N-vinyl-3,5-dimethyl-2-caprolactam, N-vinyl-4,6-dimethyl-2-caprolactam, and N-vinyl-3,5,7-trimethyl-2-caprolactam; N-vinyl amides such as N-vinylformamide, N-vinyl-N-methylformamide, N-vinyl-N-ethylformamide, N-vinylacetamide, N-vinyl-N-methylacetamide, N-vinyl-N-ethylacetamide, and N-vinylphthalimide;

[0034] Examples of hydrogel materials with a fixed charge include gel materials in which functional groups with a fixed charge have been introduced into hydrogel materials that do not have a fixed charge, and gel materials that are polymers containing monomer units with a fixed charge. Of these, gel materials that are polymers containing monomer units with a fixed charge are preferred, and copolymers of non-chargeable monomers and monomers with a fixed charge are more preferred. The fixed charge may be either a positive charge and / or a negative charge as long as the amount of charge of either the positive charge or the negative charge is greater, but it is preferably either a positive charge or a negative charge.

[0035] The monomer unit having a fixed charge is preferably a monomer unit having at least one selected from the group consisting of a sulfonic acid group, a carboxyl group, a phosphoric acid group, and an amino group, more preferably a monomer unit having a sulfonic acid group or a carboxyl group, and even more preferably a monomer unit having a carboxyl group.

[0036] Examples of the non-chargeable monomer include hydroxyethyl methacrylate, ethylene glycol diacrylate, methyl methacrylate, N-vinylpyrrolidone, dimethylacrylamide, glycerol methacrylate, vinyl alcohol, etc. The non-chargeable monomer may be used alone or in combination of two or more.

[0037] Examples of monomers having a fixed charge include carboxyl group-containing monomers such as acrylic acid, methacrylic acid, itaconic acid, 1-(2-methacryloyloxyethyl) succinate, β-carboxyethyl acrylate, itaconic acid, maleic acid, fumaric acid, crotonic acid, and isocrotonic acid; sulfonic acid group-containing monomers such as 2-acrylamido-2-methyl-propanesulfonic acid, styrenesulfonic acid, vinylsulfonic acid, (meth)acrylic acid, (meth)acrylamidopropanesulfonic acid, sulfopropyl (meth)acrylate, and (meth)acryloyloxynaphthalenesulfonic acid; phosphate group-containing monomers such as 2-hydroxyethyl acryloyl phosphate; (alkyl)aminoalkyl (meth)acrylates such as 2-dimethylaminoethyl (meth)acrylate, 2-butylaminoethyl (meth)acrylate, and aminoethyl (meth)acrylate; and amino group-containing monomers such as aminostyrene; and salts thereof. The monomers having a fixed charge may be used alone or in combination of two or more.

[0038] The polymer in the hydrogel material can be obtained, for example, by adding a polymerization initiator, a crosslinking agent, a polymerization accelerator, etc. to a monomer mixture containing monomers that constitute the hydrogel material, monomers having a fixed charge, etc., and polymerizing the mixture.

[0039] Examples of the polymerization initiator include peroxides such as lauroyl peroxide, cumene hydroperoxide, and benzoyl peroxide, which are general radical polymerization initiators, azobisvaleronitriles such as 2,2'-azobis(2,4dimethylvaleronitrile) (V-65), and azobisisobutyronitrile (AIBN).

[0040] Examples of crosslinking agents include allyl methacrylate, vinyl methacrylate, 4-vinylbenzyl methacrylate, 3-vinylbenzyl methacrylate, methacryloyloxyethyl acrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, diethylene glycol diallyl ether, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, propylene glycol dimethacrylate, dipropylene glycol dimethacrylate, butanediol dimethacrylate, trimethylolpropane trimethacrylate, 2,2-bis(p-methacryloyloxyphenyl)hexafluoropropane, 2,2-bis(m-methacryloyloxyphenyl)hexafluoropropane, 2,2- Examples of such methyl acrylates include bis(o-methacryloyloxyphenyl)hexafluoropropane, 2,2-bis(p-methacryloyloxyphenyl)propane, 2,2-bis(m-methacryloyloxyphenyl)propane, 2,2-bis(o-methacryloyloxyphenyl)propane, 1,4-bis(2-methacryloyloxyhexafluoroisopropyl)benzene, 1,3-bis(2-methacryloyloxyhexafluoroisopropyl)benzene, 1,2-bis(2-methacryloyloxyhexafluoroisopropyl)benzene, 1,4-bis(2-methacryloyloxyisopropyl)benzene, 1,3-bis(2-methacryloyloxyisopropyl)benzene, and 1,2-bis(2-methacryloyloxyisopropyl)benzene. The amount of the crosslinking agent is preferably 1 part by mass or less, more preferably 0.8 parts by mass or less, and is preferably 0.05 parts by mass or more, more preferably 0.1 parts by mass or more, per 100 parts by mass of the total amount of the monomers used in the polymerization.

[0041] Hydrogel materials can be obtained, for example, by solidifying a gel solution, or by placing a monomer mixture in a mold made of metal, glass, plastic, or the like, sealing it, and then raising the temperature in a thermostatic chamber or the like to a range of 25 to 120°C stepwise or continuously to polymerize for 5 to 120 hours. Ultraviolet light, electron beams, gamma rays, or the like may be used for polymerization. Alternatively, solution polymerization may be performed by adding water or an organic solvent to the monomer mixture.

[0042] After polymerization is complete, the molded piece is cooled to room temperature, and the resulting molded piece is removed from the mold and cut and polished as necessary. The resulting molded piece may be hydrated and swollen to form a hydrogel. Examples of the liquid (swelling liquid) used for hydration and swelling include aqueous solutions containing ions with an opposite charge to the fixed charge, which can generate an electroosmotic flow. The swelling liquid can be heated to 60 to 100°C and immersed for a certain period of time to rapidly achieve a hydrated and swollen state. Furthermore, the swelling treatment can also remove unreacted monomers contained in the polymer.

[0043] Examples of anions contained in the aqueous solution serving as the swelling liquid include amino acid ions (natural amino acid ions and unnatural amino acid ions), chloride ions, citrate ions, lactate ions, succinate ions, phosphate ions, malate ions, pyrrolidone carboxylate ions, sulfocarbonate ions, sulfate ions, nitrate ions, phosphate ions, carbonate ions, and perchlorate ions. Examples of natural amino acids include glycine, alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, threonine, serine, proline, tryptophan, methionine, cysteine, aspartic acid, glutamic acid, asparagine, glutamine, lysine, arginine, and histidine. Examples of unnatural amino acids include hydroxyproline, cystine, and thyroxine. Examples of cations contained in the aqueous solution include K+, Na+, Ca2+, and Mg2+.

[0044] Furthermore, among the materials that can be used to form the first transporter 11 and the second transporter 12, materials other than hydrogels include resins such as urethane resin, polycarbonate, acrylonitrile-butadiene-styrene (ABS) resin, phenolic resin, acrylic resin, and methacrylic resin (e.g., polyglycidyl methacrylate resin). Oxides include inorganic oxides and their derivatives, such as silicon oxide, tin oxide, zirconia oxide, titanium oxide, niobium oxide, tantalum oxide, aluminum oxide, tungsten oxide, hafnium oxide, and zinc oxide. Metals include nickel, iron, and alloys thereof. Biodegradable materials include polylactic acid-co-glycolic acid (PLGA) and PLGA-based composites, β-tricalcium phosphate, calcium carbonate, polycaprolactone, polydioxanone, hydroxyapatite, polyethylene glycol, and magnesium alloys. The first transporter 11 and the second transporter 12 may be composed of a combination of two or more of the substances listed here.

[0045] The first transporter 11 may have any structure in which the mobility of anions is greater than that of cations when a fluid is introduced into the first flow path 11a, such as a structure in which positive charges are fixed to the wall surface of the first flow path 11a, a structure in which positive charges are embedded in the surface layer, or a hydrogel containing positively charged functional groups. The second transporter 12 may have any structure in which the mobility of cations is greater than that of anions when a fluid is introduced into the second flow path 12a, such as a structure in which negative charges are fixed to the wall surface of the second flow path 12a, a structure in which negative charges are embedded in the surface layer, or a hydrogel containing negatively charged functional groups.

[0046] The storage chamber 13 is provided in communication with the first opening 11b and the second opening 12b on the end surface of one end side (the tip side of the tube) of the first transport body 11 and the second transport body 12. The storage chamber 13 has a third opening 13a on the opposite side from the first opening 11b and the second opening 12b, i.e., at the tip of the tube.

[0047] A predetermined fluid is stored inside the storage chamber 13. Fluids are also stored in the first flow path 11a and the second flow path 12a. The fluids stored in the storage chamber 13, the first flow path 11a, and the second flow path 12a may be any fluid that can be ionized into cations and anions, such as an electrolyte solution. The fluids stored in the storage chamber 13, the first flow path 11a, and the second flow path 12a may be the same type or different types.

[0048] The current / voltage application means 14 is connected to the first electrode 11c and the second electrode 12c and is capable of applying a current or a voltage between the first electrode 11c and the second electrode 12c. In the specific example shown in Fig. 1, the current / voltage application means 14 is capable of applying a current or a voltage with the second electrode 12c as a positive electrode and the first electrode 11c as a negative electrode.

[0049] Examples of materials for the first electrode 11c and the second electrode 12c include carbon materials such as carbon nanotubes, ketjen black, glassy carbon, graphene, fullerene, carbon fiber, carbon fabric, and carbon aerogel; conductive polymers such as polyaniline, polyacetylene, polypyrrole, poly(p-phenylene vinylene), polythiophene, and poly(p-phenylene sulfide); semiconductors such as silicone, germanium, indium tin oxide (ITO), titanium oxide, copper oxide, and silver oxide; and metals such as gold, platinum, titanium, aluminum, tungsten, copper, iron, and palladium. Examples of combinations of the positive electrode (cathode) and the negative electrode (anode) include combinations of a metal electrode and an oxygen electrode (metal / oxygen battery), such as a combination of aluminum and a carbon electrode (CF / CNT, an electrode in which carbon fabric is modified with carbon nanotubes).

[0050] The electroosmotic flow pump 10 is configured so that, when a current or voltage is applied between the first electrode 11c and the second electrode 12c by the current / voltage application means 14, an ionic current flows from the fluid in the first flow path 11a through the fluid stored in the storage chamber 13 and the fluid in the second flow path 12a. This causes the electroosmotic flow pump 10 to generate an electroosmotic flow in which the fluid in the first flow path 11a flows from the first opening 11b toward the storage chamber 13, and an electroosmotic flow in which the fluid in the second flow path 12a flows from the second opening 12b toward the storage chamber 13, and these electroosmotic flows cause the fluid in the storage chamber 13 to be discharged from the third opening 13a.

[0051] Next, the operation will be described. The electroosmotic pump 10 is used as follows. First, fluids are introduced into the first flow path 11a, the second flow path 12a, and the storage chamber 13. At this time, a positive charge is fixed in the first flow path 11a, and a negative charge is fixed in the second flow path 12a. In this state, a current or voltage is applied between the first electrode 11c and the second electrode 12c by the current / voltage application means 14. This causes an ionic current to flow through the fluid in the first flow path 11a and the fluid in the second flow path 12a, thereby generating an electroosmotic flow in each fluid. This also allows a predetermined fluid in the storage chamber 13 to be discharged from the third opening 13a. In this way, the electroosmotic pump 10 can simultaneously discharge fluid from both the first transporter 11 and the second transporter 12, resulting in more efficient discharge than a pump that discharges fluid from only one of them.

[0052] Electroosmotic flow pump 10 can control the flow rate of the generated electroosmotic flow by adjusting the current or voltage applied by current / voltage application means 14, and has excellent controllability over the discharge rate. Electroosmotic flow pump 10 can be used for administering medicines, but it can also be used for other applications related to the discharge of fluids. For example, when used for administering medicines, the predetermined fluid placed in storage chamber 13 can be a fluid containing the medicine to be administered.

[0053] In electroosmotic pump 10, the ion current passes through first flow path 11a, storage chamber 13, and second flow path 12a and does not leak to the outside, preventing the ion current from affecting external biological cells, etc. Furthermore, because electroosmotic pump 10 has a long, thin tube shape, it is possible to adjust the current or voltage at the proximal end and discharge the fluid from third opening 13a at the distal end. For this reason, it can be inserted into a channel of an endoscope and used, for example, to discharge a drug into the body.

[0054] In the electroosmotic flow pump 10, the current / voltage application means 14 may be capable of changing the polarity of the voltage applied to the first electrode 11c and the second electrode 12c, or may be capable of applying a current or voltage with the second electrode 12c as negative and the first electrode 11c as positive. In this case, by applying a current or voltage with the second electrode 12c as negative and the first electrode 11c as positive by the current / voltage application means 14, an ionic current flows from the fluid in the second flow path 12a through the fluid stored in the storage chamber 13 and the fluid in the first flow path 11a. This generates an electroosmotic flow in which the fluid in the first flow path 11a flows inward from the first opening 11b, and an electroosmotic flow in which the fluid in the second flow path 12a flows inward from the second opening 12b. These electroosmotic flows allow the fluid to be drawn into the storage chamber 13 through the third opening 13a. This allows the pump to be used for applications related to fluid drawing, such as sampling body fluids from living organisms. In this way, both the first transporter 11 and the second transporter 12 can simultaneously perform attraction, which allows for more efficient attraction than when only one of them performs attraction. In addition, by changing the polarity of the voltage applied by the current / voltage application means 14, it is possible to switch between ejection and attraction.

[0055] Furthermore, electroosmotic pump 10 does not necessarily have to have storage chamber 13. In this case, first opening 11b and second opening 12b can be used by directly contacting biological tissue or the like. When current or voltage is applied between first electrode 11c and second electrode 12c by current / voltage application means 14, an ionic current flows through the fluid in first flow path 11a, the fluid contained in biological tissue or the like, and the fluid in second flow path 12a, generating an electroosmotic flow in the fluid in first flow path 11a and the fluid in second flow path 12a. This also allows fluid to be directly ejected or sucked from first opening 11b and second opening 12b, respectively.

[0056] FIG. 2 shows an electroosmotic pump according to a second embodiment of the present invention. As shown in FIGS. 2(a) and 2(b), electroosmotic pump 20 is in the form of a sheet, and includes first transporter 11, second transporter 12, storage chamber 13, and current / voltage application means . In the following description, explanation of the configuration and effects that overlap with those of the electroosmotic pump 10 of the first embodiment of the present invention will be omitted.

[0057] The first transporter 11 and the second transporter 12 are each formed in the form of a thin film, and are overlapped with each other in the thickness direction to insulate the first flow path 11a and the second flow path 12a, forming a sheet-like body 21. The sheet-like body 21 has one or more communication holes 21a formed on one surface along the thickness direction so as to communicate with the first flow path 11a and the second flow path 12a without penetrating to the other surface. The storage chamber 13 is formed from the communication holes 21a of the sheet-like body 21, and the opening of the communication hole 21a formed on one surface of the sheet-like body 21 becomes the third opening 13a.

[0058] The electroosmotic flow pump 20 can discharge or suck air from the third openings 13a on one surface of the sheet-like body 21. For this reason, for example, by providing a large number of third openings 13a on one surface of the sheet-like body 21 and attaching the sheet-like body 21 so that one surface is in contact with the skin, discharge or sucking can be performed over a relatively wide area of ​​the skin surface.

[0059] FIG. 3 shows an electroosmotic pump and a kit for applying to biological tissue according to a third embodiment of the present invention. 3(a) and 3(b), electroosmotic flow pump 30 is in the form of a patch and includes first transporter 11, second transporter 12, current / voltage application means 14, and adhesive sheet 31. Note that electroosmotic flow pump 30 does not include storage chamber 13. In the following description, explanation of the configuration and effects that overlap with those of the electroosmotic pump 10 of the first embodiment of the present invention will be omitted.

[0060] First transporter 11 and second transporter 12 are attached to the adhesive surface of adhesive sheet 31 so that first opening 11b and second opening 12b are on the opposite side of the adhesive surface. Electroosmotic flow pump 30 is configured so that first transporter 11 and second transporter 12 can be attached to biological tissue 1 by adhesive sheet 31 so that first opening 11b and second opening 12b are in contact with biological tissue 1.

[0061] When first transporter 11 and second transporter 12 are attached to biological tissue 1 and a current or voltage is applied by current / voltage application means 14, electroosmotic flow pump 30 generates an ionic current through the fluid in first flow path 11a, the fluid inside biological tissue 1, and the fluid in second flow path 12a, thereby generating an electroosmotic flow in the fluid in first flow path 11a and the fluid in second flow path 12a. This also allows fluid to be ejected or sucked from first opening 11b and second opening 12b, respectively.

[0062] In this way, electroosmotic flow pump 30 can be easily used as a patch for attaching to biological tissue by simply attaching adhesive sheet 31 to biological tissue 1 such as skin. In electroosmotic flow pump 30, first transporter 11 and second transporter 12 can be arranged at positions separated from each other. There may be one or more first transporters 11 and second transporters 12. Furthermore, first transporter 11 and second transporter 12 may be attached to separate adhesive sheets 31.

[0063] The biological tissue application kit according to the embodiment of the present invention is configured in a disassembled state, with first transporter 11, second transporter 12, current / voltage application means 14, and adhesive sheet 31, so that electroosmotic flow pump 30 can be fabricated. As shown in FIG. 3 , the biological tissue application kit according to the embodiment of the present invention allows electroosmotic flow pump 30 to be easily fabricated by assembling first transporter 11, second transporter 12, current / voltage application means 14, and adhesive sheet 31. [Example]

[0064] Various tests were carried out on the electroosmotic pumps 10, 20, and 30 according to the first to third embodiments of the present invention. The reagents, materials, and devices used in the tests are as follows.

[0065] Glycidyl methacrylate (GMA, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) Trimethylolpropane trimethacrylate (TRIM, Sigma-Aldrich) Polyethylene glycol (PEG 10 kDa, Sigma-Aldrich) Diethylene glycol (DEG, manufactured by Tokyo Chemical Industry Co., Ltd.) Irgacure (Irgacure 184, manufactured by BASF SE) Parylene C (manufactured by Daisan Kasei Co., Ltd.) Polydimethylsiloxane (PDMS, SILPOT 184, manufactured by DuPont Toray Specialty Materials Co., Ltd.) Rhodamine B (Fujifilm Wako Pure Chemical Industries, Ltd.) Gellan gum (Fujifilm Wako Pure Chemical Industries, Ltd.) Triethylene glycol dimethacrylate (TEGDMA) 2-acrylamide-2-methylpropanesulfonic acid (AMPS) N,N'-methylenebisacrylamide (MBAAmM) N,N,N',N'-tetramethylethylenediamine (TEMED) Ammonium peroxodisulfate solution (APS, 10 w / v%) Fluorescein isothiocyanate-dextran (FITC dextran, average mol wt 500,000, Sigma-Aldrich) Sofras N (urethane foam) (Aion Co., Ltd.) 1xPBS(-) (Phosphate-buffered saline, Fujifilm Wako Pure Chemical Industries, Ltd.)

[0066] First, samples constituting the first transporter 11 and the second transporter 12 were prepared and tested for electroosmotic flow. The samples used in the test were hydrogel, porous elastomer (polyurethane foam), and porous resin (epoxy resin). Each sample was prepared as follows.

[0067] To prepare the hydrogels, we used 2-acrylamido-2-methylpropanesulfonic acid sodium salt (NaAMPS) as the monomer for the anionic hydrogel and (3-acrylamidopropyl) trimethylammonium chloride (APTAC) as the monomer for the cationic hydrogel. A 1.0 M monomer solution (monomer + crosslinker MBAAm + polymerization initiator Irgacure 2959 + solvent D-PBS) was prepared for each monomer, and crosslinking polymerization was performed under UV irradiation for 1 hour to prepare positively and negatively charged hydrogels.

[0068] In the following tests, agarose gel for electrophoresis (15 g / L) was used as the neutral hydrogel. This is agarose with low electroosmotic strength (electroosmotic strength (Mr): 0.1 to 0.19), and is a neutral gel with almost no electric charge.

[0069] To prepare the porous elastomer (polyurethane foam), first, Sofras was immersed in each monomer solution prepared for hydrogel preparation, and a vacuum of -0.096 MPa was applied for 1 minute to allow the solution to fully penetrate the Sofras. Next, UV irradiation was performed for 1 hour to cause cross-linking polymerization, yielding a porous elastomer filled with positively and negatively charged hydrogels.

[0070] Porous polyglycidyl methacrylate (PGMA), a type of epoxy resin, was fabricated using the porogen method. A base mixture (10 mL of GMA, 5.23 mL of TRIM, and 15.7 mL of TEGDMA) and a porogen mixture (10 g of PEG and 50 mL of 2-methoxyethanol) were mixed in a volume ratio of 6:7. The mixture was then poured into a mold. It was then polymerized under UV light (365 nm) for 1 hour. After polymerization, the PGMA was removed from the mold and stirred in a 1:1 ethanol / water mixture at 60 °C to dissolve the porogen mixture, yielding a porous PGMA plate.

[0071] The resulting PGMA was subjected to charge fixation using the following procedure. First, the PGMA was immersed in an AMPS aqueous solution (2 mL; AMPS 0.5–1.5 mmol, MBAAm 155 mg, 10 w / v% APS 100 μL, TEMED 10 μL) at 4°C for more than 8 hours to allow the solution to penetrate into the pores. Next, thermal polymerization was performed at 70°C (more than 4 hours) to obtain PAMPS-modified porous PGMA.

[0072] An electroosmotic flow generation test was conducted using the three prepared samples (hydrogel, porous elastomer, and porous resin). The test was conducted using a Franz cell with a horizontal capillary, as shown in Figure 4. For the test, each sample 51 constituting the first transporter 11 and the second transporter 12 was formed into a sheet or plate shape with a thickness of 1.0 mm, sandwiched between two chambers 52 of the Franz cell, and fixed with a jig made of acrylic board. Both chambers 52 (opening diameter 15 mm) of the Franz cell were filled with PBS buffer solution at pH 7.0, and the injection port was closed with a silicone rubber stopper 54 with an Ag / Cl wire 53 inserted therein, sealing both chambers 52. In this state, the Ag / Cl wire 53 (AgCl+e- ⇔ Ag+Cl-) was connected to a source meter 55, and a current of 0.25 to 7 mA / cm was measured.2 A DC current of 1.6 mm was applied for 15 minutes each, and the time-dependent change in the water surface position in the horizontal capillary 56 (cross-sectional diameter 1.6 mm) was measured every 5 minutes using a camera. The test was carried out while checking that no bubbles were generated from the Ag / Cl wire 53 due to the electrode reaction.

[0073] The test results for the hydrogel, porous elastomer, and porous resin samples are shown in Figures 5(a) to 5(c), respectively. As shown in Figures 5(a) to 5(c), it was confirmed that water transport due to electroosmotic flow occurred in all samples. Figure 5(a) shows the results at 1 mA / cm 2 The graph shows the time-dependent change in the cumulative amount of water transported by electroosmotic flow in negatively and positively charged hydrogels when a direct current of 100 kJ / s is applied. As shown in Figure 5(a), for both hydrogels, the transport amount is proportional to time, confirming that water is transported at a constant flow rate. Furthermore, the direction of water transport is opposite for the negatively and positively charged hydrogels, confirming that the negatively charged hydrogel has a higher transport efficiency.

[0074] Figure 5(b) shows the relationship between the flow velocity and current value of the electroosmotic flow generated in the porous elastomer filled with the negatively and positively charged hydrogels, respectively. As shown in Figure 5(b), it was confirmed that the flow velocity increased in proportion to the current density.

[0075] Figure 5(c) shows the relationship between the flow rate and current value of the electroosmotic flow generated in the PAMPS-modified porous resin (fixed negative charge). For comparison, Figure 5(c) also shows the relationship between the flow rate and current value of the electroosmotic flow generated in the unmodified porous resin. As shown in Figure 5(c), almost no electroosmotic flow was generated in the unmodified porous resin, whereas the generation of electroosmotic flow was clearly confirmed in the porous resin with fixed negative charge. [Example]

[0076] An electroosmotic flow pump 10, in which the first transporter 11 and the second transporter 12 were constructed from a charge-fixed hydrogel, was used to conduct a test of water transport by electroosmotic flow. In the test, as shown in Figure 6(a), two thin tubes constituting the first transporter 11 and the second transporter 12 were bundled together, and a storage compartment was formed by cutting out the side of the tip of each tube and integrating them. Furthermore, a stopper 58 with a glass capillary 57 inserted therethrough was inserted into the tip of the storage chamber 13, and the tip of the glass capillary 57 became the third opening 13a.

[0077] In the test, as shown in Figure 6(b), a positively charged hydrogel (A in the figure), a negatively charged hydrogel (C in the figure), and a neutral gel (N in the figure) were combined as the first transporter 11 and the second transporter 12, and the electroosmotic flow rate was calculated by measuring the amount of water moving through the glass capillary 57. Figure 6(c) shows the observation results of the glass capillary 57 when currents of 3 mA and -3 mA were applied to the AC-type electroosmotic pump 10 shown in Figure 6(b). As shown in Figure 6(c), it was confirmed that water transport proceeded at a constant flow rate, and that the flow direction was reversed when the direction of the current (polarity of the applied voltage) was changed.

[0078] Figure 6(d) shows the calculated electroosmotic flow mobility (flow rate) for each combination in Figure 6(b) when a current of 3 mA was applied. As shown in Figure 6(d), it was confirmed that almost no flow occurred when the same type of hydrogel was combined (AA type and CC type). It was also confirmed that the AC type had the highest flow rate, approximately twice that of the AN and CN types. [Example]

[0079] A test to evaluate the discharge performance (controllability) was conducted using the AC electroosmotic pump 10 shown in Figure 6(b). In the test, the fluorescent reagent rhodamine B (molecular weight: 479.02 g / mol) was used as the fluid to be discharged (fluid stored in the storage chamber 13). To minimize the effects of atmospheric and water pressure, the glass capillary 57 was held horizontally and placed in a water tank filled with liquid so that rhodamine B could be discharged. The test was conducted with and without applying a 3 mA current. Every 5 minutes, the rhodamine B concentration in the water tank was quantified to determine the transported amount (integrated) of rhodamine B.

[0080] The test results are shown in Figure 7(a). As shown in Figure 7(a), when no current was applied, the amount of Rhodamine B that leaked out was approximately 0 μg, and the influence of passive diffusion was only slightly noticeable. However, when current was applied, it was confirmed that the amount of Rhodamine B that leaked out increased linearly over time. This indicates that when current was applied, Rhodamine B was always ejected accompanied by liquid transfer, providing high controllability.

[0081] Based on the concentration of rhodamine B ejected (0.5 mg / ml), the transport efficiency was calculated from the amount of transported substance shown in FIG. 7(a) and the mobility shown in FIG. 6(d), and is shown in FIG. 7(b). As shown in FIG. 7(b), it was confirmed that the transport efficiency remained nearly 100% even after 20 minutes. This confirmed that even rhodamine B, a positively charged cation, was ejected by flow-mediated transport without being affected by electrical effects such as electrophoresis. From these results, it can be said that the electroosmotic pump 10 has versatile controllability that is not affected by the size or charge of the transported molecule itself. [Example]

[0082] A discharge test was conducted using a patch-type electroosmotic pump 30. In the test, a first transporter 11 made of a porous elastomer with a fixed negative charge and a second transporter 12 made of a porous elastomer with a fixed positive charge were used. As shown in Figure 8(a), in the test, FITC-dextran (average mol wt 500,000) was applied to a gellan gum (gel) containing PBS, and the first transporter 11 and the second transporter 12 were attached on top of it so that the first opening 11b and the second opening 12b were in contact with the gel (dextran).

[0083] In this state, a 1 mA current was applied for 20 minutes, and the boundaries between the gel and each porous elastomer were observed. Fluorescence micrographs taken at this time are shown in Figures 8(c) and (d). For comparison, Figure 8(b) shows a fluorescence micrograph taken without current application. As shown in Figure 8(b), when no current was applied, dextran migration into the gel due to diffusion was observed. In contrast, as shown in Figures 8(c) and (d), when current was applied, dextran fluorescence was observed over a wider area, confirming that large amounts of dextran were being transported by electroosmotic flow from the first transporter 11 and the second transporter 12. [Explanation of symbols]

[0084] 1. Biological tissue 10, 20, 30 Electroosmotic pump 11 First transporter 11a First flow path 11b 1st opening 11c 1st electrode 12 Secondary transporter 12a Second flow path 12b 2nd opening 12c 2nd electrode 13 Storage Room 13a 3rd opening 14 Current and voltage application means 21 Sheet-like body 21a Communication hole 31 Adhesive Sheet 51 Samples 52 Chambers 53 Ag / Cl wire 54 Silicone rubber stopper 55 SourceMeter 56 Horizontal Capillary 57 Glass Capillary 58 Stopper

Claims

[Claim 1] a first transporter having a first flow path, a first opening communicating with the first flow path, and a first electrode disposed at a position away from the first opening of the first flow path; a second transporter having a second flow path, a second opening communicating with the second flow path, and a second electrode disposed at a position away from the second opening of the second flow path; a current / voltage applying means provided so as to be able to apply a current or a voltage between the first electrode and the second electrode; the first transporter has a positive charge fixed to a wall surface of the first channel, or has a positive charge embedded in a surface layer of the first channel, or is made of a hydrogel containing a positively charged functional group; the second transporter has a negative charge fixed to a wall surface of the second flow channel, or has a negative charge embedded in a surface layer of the second flow channel, or is made of a hydrogel containing a negatively charged functional group; the first transporter is elongated, the first opening is formed at one end, and the first electrode is provided at the other end; the second transporter is elongated and provided along the first transporter with the second flow path insulated from the first flow path, the second opening is formed at one end thereof so as to be adjacent to the first opening, and the second electrode is provided at the other end thereof; The first opening and the second opening are configured to be used in contact with biological tissue, When a current or a voltage is applied between the first electrode and the second electrode by the current / voltage application means, an ion current flows through the fluid in the first flow path, the fluid inside the biological tissue, and the fluid in the second flow path, and an electroosmotic flow is generated in each of the fluids. Electroosmotic pump characterized by:

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