Method for Concentrating Analytical Solution Using Forward Osmosis Membrane, and Analytical Method

Abstract

The present invention is a concentration method for concentrating, before performing analysis using an analysis device, an analysis solution that includes an analysis solute and an analysis solvent. The concentration method is based on positive osmosis in which, using a concentration device, the analysis solution and the induction solution are brought into mutual contact via a positive osmosis membrane so that the analysis solvent within the analysis solution is removed by being allowed to pass through the positive osmosis membrane and be transferred into the induction solvent. The concentration device includes: a positive osmosis membrane module including the positive osmosis membrane; an analysis solution tank; analysis solution feed piping; an induction solution tank; and induction solution feed piping. The total of the capacity of an analysis solution fluid flow section of the positive osmosis membrane module and the capacity of the analysis solution feed piping is 500 mL or less. The concentration of the analysis solute in the analysis solution is 0.01 ppm or less, and the concentration of the analysis solute in the analysis solution after concentration is 0.02 ppm or greater.

Description

Technical Field

[0001] The present invention relates to a concentration method for concentrating an analysis solution before analysis by an analyzer, and an analysis method for analyzing the analysis solution concentrated by this concentration method.

[0002] Measurements of trace substances present in the environment such as rivers, seas, tap water, and sewage; Utilities, quality inspections, validation of equipment after cleaning, validation of containment technology, etc. in factories, etc.; Water quality inspections, component inspections, etc. in the fields of fisheries, agriculture, etc.; Various analyses are being carried out in clinical inspections using blood, urine, etc. At the time of analysis, when the concentration of the analyte (analysis solute) contained in the analysis solution is low, it is necessary to perform pretreatment (for example, concentration) of the sample before analysis to increase the concentration of the analysis solute in the sample. As pretreatment of the analysis sample, as concentration methods for increasing the concentration while avoiding denaturation, dissipation, etc. of the analysis solute, a solid phase extraction method, a concentration method using a separation membrane, etc. are known. The solid phase extraction method is a concentration method that involves a step of adsorbing an analysis solute onto an adsorbent such as an ion exchange resin and then eluting it using an appropriate organic solvent. Since this method requires a plurality of steps, the operation is complicated.

[0003] As a concentration method using a separation membrane, for example, methods using an ultrafiltration membrane, a nanofiltration membrane, a reverse osmosis membrane, a forward osmosis membrane, etc. are known, and it is a technology capable of concentrating by a simple method of directly concentrating the analysis solution. Concentration using an ultrafiltration membrane is a technique for separation using the difference in molecular weight by sieving. That is, components having a size equal to or larger than the cut-off molecular weight of the ultrafiltration membrane are retained in the analysis solution without passing through the membrane, while the solvent passes through the membrane and is separated, thereby concentrating the analysis solution. This method is effective, for example, for concentrating an analysis solution containing large molecules such as proteins as the analysis solute, and has the advantage that denaturation of the analysis solute can be avoided because heating of the sample is not required (Patent Document 1). The nanofiltration membrane can permeate the solvent in the analysis solution at the molecular level, and even by using this, the analysis solution can be concentrated without heating. Both the reverse osmosis membrane and the forward osmosis membrane can also permeate the solvent in the analysis solution at the molecular level, similar to the nanofiltration membrane. Patent Document 2 discloses a technique of introducing an analysis solution into a two-stage reverse osmosis membrane device connected in series for concentration. Further, Patent Document 3 discloses a technique of bringing the test water (analysis solution) into contact with a highly osmotic substance through a water-permeable semipermeable membrane and moving the water in the test water to the highly osmotic substance to concentrate the test water.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0005] As described above, when using a separation membrane, it becomes possible to concentrate the analysis solution by a non-heating and simple method. However, in the technique using the ultrafiltration membrane of Patent Document 1, since the analysis solute smaller than the fractional molecular weight of the membrane passes through the membrane, there is a certain limit to the types of analysis solutions that can be concentrated by this method. Also, in the technique using the reverse osmosis membrane described in Patent Document 2, high pressure is required as the driving force for concentration. Therefore, problems such as the adhesion of the analysis solute to the membrane due to pressurization in the analysis solution and the contamination of the analysis solution by the leakage from the rotating part of the pressure pump occur. In this regard, according to the technology of Patent Document 3, the driving force for concentration is the osmotic pressure difference between the analysis solution and the high osmotic pressure substance, and high pressure is not required for driving. Therefore, the fixation of the analysis solute to the membrane due to pressurization and the problems caused by the pressure pump are improved.

[0006] However, in Patent Document 3, the relationship between the "theoretical concentration ratio" (also referred to as the "volume reduction ratio" in this specification) calculated from the reduction amount of the volume of the analysis solution after concentration and the "analysis solute concentration ratio" (also referred to as the "sensitivity improvement ratio" in this specification) calculated from the concentration of the analysis solute in the analysis solution after concentration is not considered. In the so-called "pre-concentration" in which the analysis solution is concentrated so that the analysis solute concentration becomes a predetermined concentration or more before analysis, the lower the analysis solute concentration in the analysis solution before concentration, the more the influence of the loss of the analysis solute during the concentration process increases. Therefore, the deviation between the "theoretical concentration ratio" and the "analysis solute concentration ratio" tends to increase.

[0007] In Patent Document 3, moreover, the case where the analysis solution is small is not examined. According to the technology of Patent Document 3, when the analysis solution is small, the loss of the analysis solute during the concentration process is large, and it is difficult to perform effective concentration. Therefore, in the prior art, when the analysis solution is small, there is a problem that it is difficult to suppress the loss of the analysis solute during the concentration process and perform effective concentration without altering the components in the analysis solution.

[0008] The present invention has been made based on the above circumstances. Therefore, a first object of the present invention is to provide a concentration method in which the deviation between the "theoretical concentration ratio" and the "analysis solute concentration ratio" is suppressed in pre-concentration, and an analysis method of an analysis solution including the concentration method. A second object of the present invention is to provide a concentration method capable of suppressing the loss of the analysis solute during the concentration process and performing effective concentration without altering the components in the analysis solution even when the analysis solution is small, and an analysis method of an analysis solution including the concentration method.

Means for Solving the Problem

[0009] An embodiment of the present invention for achieving the above object is as follows. 《Aspect 1》A concentration method for concentrating an analysis solution containing an analysis solute and an analysis solvent before analysis by an analyzer, wherein the concentration method uses a concentration device including a forward osmosis membrane module including a forward osmosis membrane, an analysis solution tank, an analysis solution feed pipe, an inducing solution tank, and an inducing solution feed pipe, contacts the analysis solution and the inducing solution through the forward osmosis membrane, and passes the analysis solvent in the analysis solution through the forward osmosis membrane and moves it into the inducing solution Liquid for removal, which is a concentration method by the forward osmosis method, the total volume of the analysis solution passage part of the forward osmosis membrane module and the volume of the analysis solution feed pipe is 500 mL or less, the concentration of the analysis solute in the analysis solution is 0.01 ppm or less, and the concentration of the analysis solute in the concentrated analysis solution is 0.02 ppm or more, concentration method. 《Aspect 2》The effective membrane area M of the forward osmosis membrane is 0.1 cm 2 or more and 0.20 m 2 or less, and the concentration method according to Aspect 1. 《Aspect 3》A concentration method for concentrating an analysis solution containing an analysis solute and an analysis solvent before analysis by an analyzer, wherein the concentration method contacts the analysis solution and the inducing solution through the forward osmosis membrane, and passes the analysis solvent in the analysis solution through the forward osmosis membrane and moves it into the inducing solution Liquid for removal, which is a concentration method by the forward osmosis method, the analysis solution is not circulated during concentration, and the amount Vf of the analysis solution used in the concentration method is 0.01 mL or more and 50 mL or less, concentration method. 《Aspect 4》The amount Vf (L) of the analysis solution and the effective membrane area M (m 2The ratio (Vf / M) to is 0.01 L / m 2 200 L / m or more 2 The concentration method according to aspect 3, which is less than that. 《Aspect 5》The effective membrane area M of the forward osmosis membrane is 0.001 cm 2 500 cm or more 2 The concentration method according to aspect 3, which is less than or equal to that. 《Aspect 6》The viscosity of the analysis solution is less than 5,000 mPa·sec, and the concentration method according to aspect 3. 《Aspect 7》To the forward osmosis membrane with an effective membrane area of M (m 2 ), an aqueous solution Vr (L) of brilliant blue R with a concentration of 10 ppm is contacted under the condition of Vr / M = 1.8 L / m 2 After standing at room temperature (25°C) for 24 hours in a state of contact, the amount of brilliant blue R contained in the recovered aqueous solution of brilliant blue R is 80% or more of the amount of brilliant blue R contained in the aqueous solution of brilliant blue R before contact with the forward osmosis membrane. The concentration method according to aspect 3. 《Aspect 8》The forward osmosis membrane is a membrane containing one or more selected from the group consisting of polyethersulfone, polysulfone, polyketone, polyetheretherketone, polyphenylene ether, polyvinylidene fluoride, polyacrylonitrile, polyethylene, polyimine, polyimide, polybenzoxazole, polybenzimidazole, sulfonated tetrafluoroethylene, cellulose acetate, and polyamide. The concentration method according to any one of aspects 1 to 7. 《Aspect 9》The forward osmosis membrane is a composite membrane including a porous support layer and a separation active layer on one or both sides of the porous support layer. The concentration method according to any one of aspects 1 to 7. 《Aspect 10》The porosity of the porous support layer is 30% or more. The concentration method according to aspect 9. 《Aspect 11》The separation active layer is a layer containing polyamide. The concentration method according to aspect 9. 《Aspect 12》The forward osmosis membrane is in a hollow fiber shape, a tubular shape, or a flat membrane shape. The concentration method according to any one of aspects 1 to 7. 《Aspect 13》The concentration method according to Aspect 12, wherein the inner diameter of the hollow fiber or tubular forward osmosis membrane is 20 μm or more and 5,000 μm or less. 《Aspect 14》The concentration method according to any one of Aspects 1 to 7, wherein the forward osmosis membrane is in a hollow fiber or tubular shape and has a separation active layer on the inner surface of the hollow fiber or tubular porous support layer. 《Aspect 15》The concentration method according to Aspect 14, wherein the analysis solution is passed or disposed in the inner space of the hollow fiber or tubular forward osmosis membrane, and the inducing solution is passed or disposed outside the hollow fiber or tubular forward osmosis membrane. 《Aspect 16》The concentration method according to any one of Aspects 1 to 7, wherein the forward osmosis membrane is in a flat membrane shape and has a separation active layer on one surface of the flat membrane porous support layer. 《Aspect 17》The concentration method according to Aspect 16, wherein the analysis solution is passed or disposed on the separation active layer side of the flat membrane forward osmosis membrane, and the inducing solution is passed or disposed on the porous support layer side of the forward osmosis membrane. 《Aspect 18》The concentration method according to any one of Aspects 1 to 7, wherein the inducing solution is a solution containing one or more selected from the group consisting of salts, organic acids, sugars, alcohols, glycols, organic polymers, and organic solvents. 《Aspect 19》The concentration method according to Aspect 1 or 2, wherein the sensitivity improvement rate expressed as the ratio of the concentration of the analysis solute contained in the concentrated analysis solution to the concentration of the analysis solute contained in the analysis solution before concentration is 2.0 or more and less than 2,000 times. 《Aspect 20》The concentration method according to any one of Aspects 3 to 7, wherein the sensitivity improvement rate expressed as the ratio of the concentration of the analysis solute contained in the concentrated analysis solution to the concentration of the analysis solute contained in the analysis solution before concentration is 1.5 or more and less than 2,000 times. 《Aspect 21》An analysis method in which an analysis solution containing an analysis solute and an analysis solvent is concentrated by the concentration method according to any one of Aspects 1 to 7 and then subjected to instrumental analysis. Aspect 22: The analysis method according to Aspect 21, wherein the instrumental analysis is selected from the group consisting of liquid chromatography, gas chromatography, inductively coupled plasma analysis, atomic absorption analysis, and ion chromatography. Aspect 23: A concentration kit for performing the concentration method according to any one of Aspects 3 to 7, wherein the concentration kit has a configuration in which the analysis solution and the induction solution are brought into contact with each other through a forward osmosis membrane, and the analysis solvent in the analysis solution is passed through the forward osmosis membrane and moved into the induction solution Liquid and removed, the concentration kit does not include a circulation means, and the amount Vf of the analysis solution that can be filled in the concentration kit is 0.01 mL or more and 50 mL or less. Concentration kit. Aspect 24: The concentration kit according to Aspect 23, wherein the forward osmosis membrane is in a hollow fiber shape or a tubular shape, and has a configuration in which an analysis solution-containing forward osmosis membrane, in which the analysis solution is disposed in the inner space of the hollow fiber-shaped or tubular forward osmosis membrane, can be immersed in the induction solution. Concentration kit according to Aspect 23. Aspect 25: The concentration kit according to Aspect 23, wherein the forward osmosis membrane is in a flat membrane shape, and has one or more partition structures for storing the analysis solution on one surface of the flat membrane-shaped forward osmosis membrane, the analysis solution stored in the partition structure can be in contact with one surface of the flat membrane-shaped forward osmosis membrane, and the induction solution can be in contact with the other surface of the flat membrane-shaped forward osmosis membrane. Concentration kit according to Aspect 23.

Advantages of the Invention

[0010] According to the present invention, first, a concentration method in which the deviation between the "theoretical concentration factor" and the "analysis solute concentration factor" is suppressed in preconcentration, and an analysis method for an analysis solution including the concentration method are provided. Second, even when the amount of the analysis solution is small, there is provided a concentration method capable of suppressing loss of an analysis solute during a concentration process and performing effective concentration without alteration of components in the analysis solution, and an analysis method of an analysis solution including the concentration method.

Brief Description of Drawings

[0011]

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Mode for Carrying Out the Invention

[0012] 《Concentration Method》 The present inventors focused on concentration using a forward osmosis membrane as a technique capable of concentrating an analytical solution without heating or pressurization, and conducted a detailed examination of the application conditions for concentrating a dilute or small amount of an analytical solution. As a result, a novel concentration method was achieved from two viewpoints.

[0013] The concentration method in the first aspect of the present invention is A concentration method for concentrating an analytical solution containing an analytical solute and an analytical solvent before analysis by an analytical apparatus, The concentration method is Using a concentration apparatus including a forward osmosis membrane module including a forward osmosis membrane, an analytical solution tank, an analytical solution feed pipe, an inducing solution tank, and an inducing solution feed pipe, Contacting the analytical solution and the inducing solution through the forward osmosis membrane, and passing the analytical solvent in the analytical solution through the forward osmosis membrane and moving it into the inducing solution Liquid To remove it, it is a concentration method by the forward osmosis method, The total volume of the analytical solution passage portion of the forward osmosis membrane module and the volume of the analytical solution feed pipe is 500 mL or less, The concentration of the analytical solute in the analytical solution is 0.01 ppm or less, and the concentration of the analytical solute in the concentrated analytical solution is 0.02 ppm or more, It is a concentration method. Here, the effective membrane area M of the forward osmosis membrane may be 0.1 cm 2 Or more and 0.20 m 2 Or less.

[0014] The inventors of the present invention have carefully studied the phenomenon of deviation between the "theoretical concentration ratio" and the "analytical solute concentration ratio" in pre-concentration. As a result, they have found a peculiar phenomenon that when the concentration of the analytical solute in the analytical solution before concentration is below a certain value, the deviation between the "theoretical concentration ratio" and the "analytical solute concentration ratio" decreases, leading to the first aspect of the present invention. In this concentration method, it can be particularly efficiently implemented when the effective membrane area of the forward osmosis membrane is within a predetermined range.

[0015] The concentration method according to the second aspect of the present invention is a concentration method for concentrating an analytical solution containing an analytical solute and an analytical solvent before analysis by an analytical device, wherein the concentration method comprises bringing the analytical solution into contact with an inducing solution through a forward osmosis membrane, and passing the analytical solvent in the analytical solution through the forward osmosis membrane and moving it into the inducing solution Liquid for removal, which is a concentration method by the forward osmosis method, wherein the analytical solution is not circulated during concentration, and the amount Vf of the analytical solution used in the concentration method is 0.01 mL or more and 50 mL or less, which is a concentration method. In this concentration method, the ratio (Vf / M) of the amount Vf (L) of the analytical solution to the effective membrane area M (m 2 ) of the forward osmosis membrane is preferably 0.01 L / m 2 or more and less than 200 L / m 2 .

[0016] The inventors of the present invention have also carefully studied the phenomenon that when concentrating using a membrane in the case of a small amount of the analytical solution, the analytical solute in the analytical solution is lost and effective concentration cannot be achieved. The concentration method using a forward osmosis membrane is applied to the concentration of a relatively large amount of the analytical solution. In this case, usually, the concentration operation is performed in a mode where the analytical solution is circulated so as to move relative to the forward osmosis membrane. However, the inventors have found that when the amount of the analysis solution is small, effective concentration can be achieved without circulating the analysis solution, leading to the second aspect of the present invention. In this concentration method, it can be particularly effectively carried out when the area of the forward osmosis membrane is within a specific range with respect to the amount of the analysis solution.

[0017] Hereinafter, each element of the concentration method of the present invention will be described in order. In the following description, matters not specifically noted are applicable to both the first aspect and the second aspect of the present invention.

[0018] 〈Analysis solution〉 The analysis solution concentrated by the concentration method of the present invention contains an analysis solute and an analysis solvent. Examples of the analysis solute in the present invention include perfluoroalkyl compounds and polyfluoroalkyl compounds such as perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS); environmental hormones such as polychlorinated biphenyls and dioxins; odor substances such as 2-methylisoborneol, 2,4,6-trichloroanisole, 2,4,6-tribromoanisole, geosmin, 1-octen-3-ol, and 3-octanone; low-molecular organic compounds such as dichloromethane, chloroform, tetrahydrofuran, ethyl acetate, isopropyl acetate, methanol, ethanol, ammonia, dimethyl sulfoxide, and dimethylformamide; biological substances and biomarkers such as metabolites, peptides (such as oligopeptides), amino acids, proteins, nucleic acids, and exosomes; pharmaceuticals and cosmetics such as low-molecular pharmaceuticals, pharmaceutical intermediates, antibiotics, vitamins, and cosmetic intermediates; manufacturing intermediates of the pharmaceuticals and the cosmetics; manufacturing raw materials of the pharmaceuticals and the cosmetics; pigments; agricultural chemicals; harmful substances present in the environment such as carcinogenic substances; drugs such as narcotics; salts; ions; radioactive substances such as iodine-131, cesium-134, cesium-137, strontium-90, and plutonium-239; viruses such as coronaviruses; bacteria; pathogens; and the like.

[0019] Low-molecular-weight pharmaceuticals refer to synthetic pharmaceuticals with a molecular weight generally below 500. Examples of low-molecular-weight pharmaceuticals include immunosuppressive drugs such as cyclosporine, mizoribine, cyclophosphamide, and azathioprine; tyrosine kinase inhibitors such as gefitinib, erlotinib, and osimertinib; FLT tyrosine kinase inhibitors such as gilteritinib; anaplastic lymphoma kinase inhibitors such as crizotinib, ceritinib, and alectinib; Janus kinase inhibitors such as tofacitinib, baricitinib, and ruxolitinib; PARP inhibitors such as olaparib and niraparib; Raf kinase inhibitors such as sorafenib and vemurafenib; MEK inhibitors such as trametinib; CDK inhibitors such as palbociclib; proteasome inhibitors such as bortezomib and carfilzomib, etc.

[0020] The analytical solvents in the present invention include water, organic solvents, or mixtures thereof. Examples of organic solvents include alcohols, esters, ethers, aprotic polar compounds, aromatic compounds, aliphatic compounds, chlorinated hydrocarbons, ketones, aldehydes, etc.

[0021] Specific examples of the analysis solvent include water; alcohols such as methanol, ethanol, normal propanol, isopropanol, normal butanol, sec-butanol, t-butanol, hexafluoroisopropyl alcohol, etc.; esters such as methyl formate, ethyl formate, methyl acetate, ethyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, etc.; ethers such as tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, cyclopentyl methyl ether, t-butyl methyl ether, anisole, 1,2-dimethoxyethane, etc.; aprotic polar compounds such as acetonitrile, dimethylacetamide, N-methylpyrrolidone, N,N-dimethylformamide, dimethyl sulfoxide, nitromethane, sulfolane, etc.; aromatic compounds such as benzene, toluene, xylene, cumene, pyridine, etc.; aliphatic compounds such as heptane, hexane, cyclohexane, methylcyclohexane, tetralin, etc.; chlorinated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,2-dichloroethene, 1,1,1-trichloroethane, 1,1,2-trichloroethene, chlorobenzene, etc.; ketones such as acetone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, etc.; aldehydes such as formaldehyde, acetaldehyde, propionaldehyde, butanal, acrolein, benzaldehyde, furfural, vanillin, etc. Each is listed respectively.

[0022] From the perspective of sample handling, the analysis solvent is preferably one or more selected from water and alcohols.

[0023] In the first aspect of the present invention, the concentration of the analyte in the analysis solution before concentration is 0.01 ppm or less. When the concentration of the analyte in the analysis solution before concentration is 0.01 ppm or less, the deviation between the "theoretical concentration magnification" and the "analyte concentration magnification" in the concentrated analysis solution is suppressed. In the first aspect of the present invention, the concentration of the analyte in the analysis solution before concentration may be 0.0099 ppm or less, 0.0098 ppm or less, 0.0095 ppm or less, 0.0090 ppm or less, or 0.0085 ppm or less. On the contrary, from the viewpoint of ensuring the effectiveness of the analysis to which the analysis solution after concentration is subjected, the concentration of the analyte in the analysis solution before concentration may be 0.01 ppt (parts per trillion) or more, 0.1 ppt or more, 1.0 ppt or more, 10 ppt or more, 100 ppt or more, 0.001 ppm or more, 0.0020 ppm or more, 0.0030 ppm or more, or 0.0050 ppm or more. When the analysis solution before concentration is a dilute solution so dilute that the concentration of the analyte contained therein cannot be detected, for example, the concentration of the analyte in the analysis solution before concentration can be known by the following method: Preparing a dilute solution with a known concentration using the same analyte and analysis solvent as the dilute analysis solution with an unknown concentration; Concentrating the obtained dilute solution by changing the concentration factor by the method of the present invention; Calculating the "theoretical concentration factor" and the "analyte concentration factor" for each of the obtained concentrates, and creating a calibration curve between the two; and Applying the above calibration curve to the concentrate of the dilute analysis solution with an unknown concentration.

[0024] On the other hand, in the second aspect of the present invention, the concentration of the analyte in the liquid-separated solution may be, for example, 0.1 ppt (parts per trillion) or more and 5 mass% (50,000 ppm (parts per million), equal to "μg / mL") or less, 1.0 ppt or more and 1 mass% (10,000 ppm) or less, 10 ppt or more and 5,000 ppm or less, 100 ppt or more and 1,000 ppm or less, or 200 ppt or more and 500 ppm or less.

[0025] The viscosity of the analysis solution in the present invention is preferably less than 5,000 mPa·sec. The method of the present invention can perform effective concentration when applied to an analysis solution with a relatively low viscosity. From this perspective, the viscosity of the analysis solution may be 4,000 mPa·sec or less, 3,000 mPa·sec or less, 2,000 mPa·sec or less, 1,000 mPa·sec or less, 500 mPa·sec or less, 100 mPa·sec or less, 50 mPa·sec or less, 10 mPa·sec or less, or 5 mPa·sec or less. The viscosity of the analysis solution may be 0.1 mPa·sec or more or 0.5 mPa·sec or more.

[0026] Specific examples of the analysis solution in the present invention include, for example, natural waters such as pond water, river water, lake water, and seawater; treated waters such as treated water from a water purification plant, treated water from a sewage treatment plant, drainage from a power plant, tap water, sewage, agricultural water, and fishery water for aquaculture; industrial wastewater, cleaning rinse solutions; biological waters such as blood, urine, tears, and sweat; test waters for drug testing; and process solutions in pharmaceutical manufacturing, cosmetic manufacturing, chemical manufacturing, etc.

[0027] In the first aspect of the present invention, the volume Vf of the analysis solution is arbitrary. However, in the first aspect of the present invention, the volume Vf of the analysis solution may be 0.1 mL or more and 10 L or less, 0.12 mL or more and 8 L or less, 0.14 mL or more and 6 L or less, 0.16 mL or more and 5 L or less, 0.18 mL or more and 1 L or less, 0.2 mL or more and 500 mL or less, or 0.3 mL or more and 300 mL or less.

[0028] On the other hand, in the second aspect, the volume Vf of the analysis solution is 0.01 mL or more and 50 mL or less. In the second aspect of the present invention, the volume Vf of the analysis solution is 50 mL or less. If the volume Vf of the analysis solution is 50 mL or less, effective concentration can be achieved by the concentration method of the second aspect of the present invention. Also, from the perspective of ensuring effective concentration, the volume Vf of the analysis solution is 0.01 mL or more.

[0029] 〈Induction solution〉 In the concentration method of the present invention, the induction solution has an osmotic pressure higher than that of the analysis solution, and has a function of moving the analysis solvent in the analysis solution to the induction solution side using the osmotic pressure difference between the induction solution and the analysis solution as a driving force. As long as the induction solution has the above function, its composition may be arbitrary. However, the induction solution in the present invention is typically composed of an inducer dissolved in an induction solvent. The osmotic pressure of the induction solution composed of an inducer dissolved in a solvent can be estimated by the van't Hoff equation shown in the following formula (3). Π = CRT (1) In the formula (1), Π is the osmotic pressure (Pa), C is the molar concentration (mol / L) of the inducer, and R is the gas constant (Pa·L / (K·mol)).

[0030] The induction solution in the present invention is preferably a solution containing one or more selected from the group consisting of salts, organic acids, sugars, alcohols, glycols, organic polymers, and organic solvents.

[0031] Examples of the inducer in the induction solution include salts, organic acids, sugars, alcohols, glycols, organic polymers, organic solvents, etc. Therefore, the induction solution in the present invention may be a solution containing one or more selected from salts, organic acids, sugars, alcohols, glycols, organic polymers, organic solvents, etc. Preferred salts include inorganic salts, salts of organic acids, etc. Specific examples of the inducer include, for example, as inorganic salts, for example, sodium chloride, magnesium chloride, calcium chloride, sodium sulfate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydrogen sulfate, potassium hydrogen sulfate, magnesium sulfate, potassium sulfate, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, etc.; as organic acids, for example, formic acid, acetic acid, propionic acid, citric acid, fluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, oxalic acid, gluconic acid, lactic acid, glycolic acid, glyceric acid, etc.; salts of the above organic acids; as sugars, for example, common sugars such as sucrose, fructose, glucose, etc.; special saccharides such as oligosaccharides and rare sugars; as alcohols, for example, methanol, ethanol, 1-propanol, 2-propanol, etc.; as glycols, ethylene glycol, propylene glycol, etc.; as organic polymers, for example, polyethylene oxide, polypropylene oxide, etc., and copolymers thereof, etc.; as organic solvents, for example, toluene, benzene, xylene, etc. As the inducer in the induction solution in the present invention, preferably, an induction solvent having a high osmotic pressure Liquid is an inorganic salt from the viewpoint of obtaining.

[0032] As the induction solvent in the induction solution, for example, one or more selected from water and organic solvents can be used. Specifically, it can be appropriately selected and used from the above specific examples as the analysis solvent in the analysis solution. However, from the viewpoint of avoiding the mixing of foreign solvents into the analysis solution, the induction solvent is preferably the same type of solvent as the analysis solvent. The concentration of the inducer in the induction solution may be appropriately set so as to exhibit a desired osmotic pressure.

[0033] 〈Forward osmosis membrane〉 The forward osmosis membrane used in the concentration method of the present invention has a function of removing the analysis solvent in the analysis solution from the analysis solution and transferring it to the induction solution by using the osmotic pressure difference between the analysis solution and the induction solution as a driving force. Therefore, the forward osmosis membrane used in the concentration method of the present invention is preferably a semi-permeable membrane having a high permeation rate of the analysis solvent in the analysis solution and a low permeation rate of the inducer in the induction solution. When the forward osmosis membrane has such permeation performance, it is preferable because effective concentration can be performed while avoiding contamination of the induction solution into the analysis solvent when concentrating the analysis solution.

[0034] In the first aspect of the present invention, the effective membrane area of the forward osmosis membrane is preferably 0.1 cm 2 or more and 0.20 m 2 (2,000 cm 2 ) or less. When the effective membrane area of the forward osmosis membrane is 0.1 cm 2 or more, concentration in a short time becomes possible. When the effective membrane area is 0.20 m 2 or less, the workability of concentrating a small amount of the analysis solution is improved. The effective membrane area of the forward osmosis membrane is more preferably 1.0 cm 2 or more and 0.1 m 2 (1,000 cm 2 ) or less, and even more preferably 5.0 cm 2 or more and 0.1 m 2 or less. A forward osmosis membrane having an effective membrane area of 0.1 m 2 or less can be applied to a portable mobile type small forward osmosis membrane module, which is preferable from the viewpoint of workability.

[0035] On the other hand, in the second aspect of the present invention, the effective membrane area M of the forward osmosis membrane is preferably 0.001 cm 2 or more and 500 cm 2 or less. When the effective membrane area of the forward osmosis membrane is 0.001 cm 2 or more, the workability of concentration is improved. Further, when the effective membrane area of the forward osmosis membrane is 500 cm 2 or less, it can be applied to a portable mobile type small forward osmosis membrane module, and concentration work at the sampling site of the analysis solution becomes possible, which is preferable.

[0036] In the second aspect of the present invention, it can also be carried out particularly effectively when the area of the forward osmosis membrane is within a specific range with respect to the amount of the analysis solution. Specifically, the effective surface area M (m 2 ) of the forward osmosis membrane is such that the ratio (Vf / M) of the amount Vf (L) of the analysis solution to the effective membrane area M (m 2 ) of the forward osmosis membrane is preferably set within the range of 0.01 L / m 2 or more and less than 200 L / m 2 . When this ratio Vf / M is 0.01 L / m 2 or more, the handling workability of the analysis solution when concentrating a small amount of the analysis solution is improved. Further, when the ratio Vf / M is less than 200 L / m 2 , concentration in a short time becomes possible. The ratio Vf / M is more preferably 0.05 L / m 2 or more and 150 L / m 2 or less, still more preferably 0.1 L / m 2 or more and 100 L / m 2 or less, particularly preferably 0.35 L / m 2 or more and 50 L / m 2 or less, and especially preferably 0.5 L / m 2 or more and 15 L / m 2 or less.

[0037] The effective membrane area of the forward osmosis membrane refers to the area of the portion of the forward osmosis membrane through which the analysis solution can come into contact with the induction solution via the forward osmosis membrane. In the case of a forward osmosis membrane modularized as described later, the portion covered with an adhesive for fixing to the module is not included in the effective membrane area.

[0038] The shape of the forward osmosis membrane used in the concentration method of the present invention is preferably a hollow fiber shape, a tubular shape, or a flat membrane shape. Here, the "hollow fiber shape" means the shape of a hollow tube having an outer diameter of generally 5 mm or less, and the "tubular shape" means the shape of a hollow tube having an outer diameter of generally more than 5 mm. When the forward osmosis membrane is in the form of hollow fibers or tubular, the inner diameter of the forward osmosis membrane is preferably 20 μm or more and 5,000 μm or less, more preferably 50 μm or more and 3,000 μm or less, still more preferably 100 μm or more and 2,000 μm or less, and particularly preferably 500 μm or more and 1,000 μm or less.

[0039] In the second aspect of the present invention, since the analysis solution subjected to the method of the present invention is relatively small in amount, the forward osmosis membrane is preferably made of a material to which organic compounds hardly adsorb. This requirement is quantitatively ensured by satisfying the brilliant blue R recovery rate measured under the following conditions. To a forward osmosis membrane with an effective membrane area of M (m 2 ), an aqueous solution Vr (L) of brilliant blue R with a concentration of 10 ppm is contacted under the condition of Vr / M = 1.8 L / m 2 and left standing at room temperature (25°C) for 24 hours. Then, the amount of brilliant blue R contained in the recovered aqueous solution of brilliant blue R is 80% or more of the amount of brilliant blue R contained in the aqueous solution of brilliant blue R before contact with the forward osmosis membrane. In the concentration method of the present invention, when using a forward osmosis membrane showing such a brilliant blue R recovery rate, the analysis solute contained in the analysis solution is suppressed from adsorbing to the forward osmosis membrane, so that highly efficient concentration without loss of the analysis solute becomes possible. From this aspect, the above brilliant blue R recovery rate is more preferably 90% or more.

[0040] The forward osmosis membrane used in the concentration method of the present invention is not limited in its material as long as it has the above-mentioned performance, shape, and size. However, the forward osmosis membrane is preferably a membrane containing one or more selected from the group consisting of, for example, polyethersulfone, polysulfone, polyketone, polyetheretherketone, polyphenylene ether, polyvinylidene fluoride, polyacrylonitrile, polyethylene, polyimine, polyimide, polybenzoxazole, polybenzimidazole, sulfonated tetrafluoroethylene, cellulose acetate, and polyamide.

[0041] A preferred forward osmosis membrane in the present invention is a composite membrane comprising a porous support layer and a separation active layer on one or both sides of the porous support layer. The materials constituting the porous support layer and the separation active layer are each selected from the materials exemplified above. The porous support layer and the separation active layer may be made of the same material or may be made of different materials. From the viewpoint of ensuring the design freedom of the forward osmosis membrane, it is preferable that the porous support layer and the separation active layer are made of different materials.

[0042] (porous support layer) The porous support layer plays a role of imparting strength to the separation functional layer. The porous support layer may have separation performance for particles insoluble in the solvent, etc., but preferably does not substantially have separation performance for ions dissolved in the solvent, etc. The porous support layer is a layer having fine through-holes (pores). The pore diameter of the pores in the porous support layer is preferably 0.001 μm or more and 0.2 μm or less, more preferably 0.005 μm or more and 0.1 μm or less, as the average pore diameter of the surface openings. The structure in the thickness direction of the porous support layer is preferably as sparse as possible while maintaining strength in order to reduce the permeation resistance of the permeate. The sparse structure is preferably any of, for example, a network structure, a finger-like void, etc., or a mixed structure thereof.

[0043] The shape of the porous support layer may be set to conform to the desired shape of the forward osmosis membrane. The porous support layer may be, for example, a hollow fiber shape, a tubular shape, a flat membrane shape, etc.

[0044] The material of the porous support layer is preferably selected from the materials exemplified above, and more preferably formed of a resin. Examples of resins include polysulfone, polyethersulfone, polyketone, polyamide, polyimide, polyester, cellulose-based polymers, vinyl polymers, polyphenylene sulfide, polyphenylene sulfide sulfone, polyphenylene sulfone, polyphenylene oxide, polybenzoxazole, polybenzimidazole, etc. These homopolymers or copolymers can be used alone or in a blend of two or more. In addition, derivatives having an arbitrary functional group in the main chain, side chain, or terminal of these polymers can also be used as the resin in the present embodiment.

[0045] Specific examples of the resin are as follows. Examples of cellulose-based polymers include cellulose acetate, cellulose nitrate, etc. Examples of vinyl polymers include polyethylene, polypropylene, polyvinyl chloride, chlorinated polyvinyl chloride, polyvinyl alcohol, polyvinylidene fluoride, polyacrylonitrile, etc. Each can be listed.

[0046] Among those exemplified above, in particular, it is preferable to use one or more selected from polysulfone, polyacrylonitrile, polyamide, polyimide, polyester, polyvinyl alcohol, polyphenylene sulfide sulfone, polyphenylene sulfone, polyphenylene sulfide, polyethersulfone, polyvinylidene fluoride, cellulose acetate, polyketone, polybenzoxazole, polybenzimidazole, polyvinyl chloride, chlorinated polyvinyl chloride, and polyethylene. More preferably, cellulose acetate, polysulfone, polyethersulfone, polyketone, polybenzoxazole, polybenzimidazole, polyacrylonitrile, or polyethylene can be mentioned. Among these materials, polysulfone or polyethersulfone is preferably used because of its high chemical, mechanical, and thermal stability, wide spread, easy availability, and easy molding.

[0047] The thickness of the porous support layer is preferably 50 μm or more and 1,000 μm or less, more preferably 75 μm or more and 500 μm or less, and still more preferably 100 μm or more and 400 μm or less, from the viewpoints of strength and compactness when applied to a small amount of analysis solution. The porosity of the porous support layer is preferably 30% by volume or more from the viewpoint of accelerating mass transfer within the porous support layer. When the mass transfer within the porous support layer is high, it is preferable because a high osmotic pressure can be maintained through the separation active layer and efficient concentration can be achieved. On the other hand, from the viewpoint of physical strength, the porosity of the porous support layer is preferably 97% by volume or less.

[0048] (Separation active layer) The separation active layer substantially undertakes the solute separation function in the forward osmosis membrane. More specifically, it undertakes the function of separating the solvent in the liquid mixture from the solutes such as ions dissolved in this solvent. The separation active layer may exist on only one side of the porous support membrane or on both sides of the support membrane. However, the forward osmosis membrane used in the concentration method of the present invention is expected to have the function of separating the analysis solvent and the analysis solute in the analysis solution, allowing the analysis solution to pass through but not allowing the analysis solute to pass through. Therefore, the separation active layer preferably exists on the side surface of the porous support membrane that contacts the analysis solution, and that is sufficient. Therefore, the separation active layer may exist on only one side of the porous support membrane.

[0049] When the forward osmosis membrane is in a hollow fiber shape or a tubular shape, the separation active layer preferably exists on the inner surface of the hollow fiber-shaped or tubular porous support layer. When the separation active layer is disposed inside the porous support layer, it is possible to avoid the loss of the separation active layer due to rubbing between the forward osmosis membranes during concentration, which is preferable. In this case, it is preferable to pass or dispose the analysis solution in the inner space of the hollow fiber-shaped or tubular forward osmosis membrane, and to pass or dispose the induction solution outside the hollow fiber-shaped or tubular forward osmosis membrane. On the one hand, when the forward osmosis membrane is in the form of a flat membrane, the separation active layer preferably exists on one side surface of the flat porous support layer. In this case, it is preferable to pass or place the analysis solution on the separation active layer side of the flat forward osmosis membrane, and to pass or place the induction solution on the porous support layer side of the forward osmosis membrane.

[0050] The material of the separation active layer is preferably selected from the materials exemplified above, and particularly preferably formed of polyamide. The separation active layer composed of polyamide is preferably a polycondensation product of a polyfunctional amine and a polyfunctional acid halide. The separation active layer composed of polyamide is preferably formed by performing interfacial polycondensation on the surface of the porous support using an aqueous solution containing a polyfunctional amine and a solution containing a polyfunctional acid halide. The organic solvent in the organic solvent solution containing the polyfunctional acid halide is preferably an organic solvent immiscible with water. The method for forming the separation active layer composed of polyamide will be described in detail later.

[0051] The thickness of the separation active layer is preferably as thin as possible without pinholes. However, in order to maintain mechanical strength, it is desirable to have an appropriate thickness. Considering film formation stability, water permeation resistance, etc., the thickness of the separation active layer is preferably 0.01 to 3 μm, more preferably 0.1 to 1 μm, and still more preferably 0.1 to 0.8 μm.

[0052] (Method for manufacturing a forward osmosis membrane) Next, among the forward osmosis membranes used in the concentration method of the present invention, the manufacturing methods of a hollow fiber forward osmosis membrane having a separation active layer composed of polyamide on the inner surface of a hollow fiber-shaped porous support layer and a flat forward osmosis membrane having a separation active layer composed of polyamide on one side surface of a flat porous support layer, which are preferred embodiments, will be described in order.

[0053] (Method for manufacturing a hollow fiber forward osmosis membrane) First, a hollow fiber-shaped porous support layer is manufactured. The hollow fiber support layer made of a hollow fiber-shaped porous support can be manufactured by known dry-wet film forming methods, melt film forming methods, wet film forming methods, etc. using a material selected from the aforementioned resins. Among these, a dry-wet spinning method is preferably used in which a spinning dope obtained by dissolving a resin (polymer) in a solvent and an internal coagulation liquid are discharged from a double annular nozzle (spinning orifice), allowed to travel through the hollow, and then coagulated in a coagulation bath containing an external coagulation liquid to form a hollow fiber-shaped membrane. The obtained hollow fibers may be wound around a winder and cut to a predetermined length for use. When forming the hollow fiber-shaped porous support layer, for example, as described above, a double orifice is used, and the spinning dope is discharged from the outer annular orifice and the internal coagulation liquid is discharged from the inner orifice. As the internal coagulation liquid, for example, an aqueous solution containing one or more additives selected from alcohols, ethylene glycols, and amide solvents can be used. As the external coagulation liquid used as the coagulation bath, one or more selected from water, a non-solvent of the resin constituting the porous support layer, etc. can be used.

[0054] By forming a separation active layer composed of polyamide on the inner surface of the hollow fiber-shaped porous support layer obtained as described above, a suitable hollow fiber forward osmosis membrane can be obtained. As described above, the separation active layer composed of polyamide can be formed by performing interfacial polycondensation on the inner surface of the porous support layer using an aqueous solution containing a polyfunctional amine and an organic solvent solution containing a polyfunctional acid halide. As a preferable method for forming the separation active layer in the present embodiment, for example, a method of passing a first solution containing a polyfunctional amine and a second solution containing a polyfunctional acid halide through the inner space of the porous support layer in this order can be mentioned.

[0055] A polyfunctional amine is an amine having at least two of primary amino groups and secondary amino groups in one molecule. For example, aromatic polyfunctional amines such as o-phenylenediamine, m-phenylenediamine, p-phenylenediamine, o-xylylenediamine, m-xylylenediamine, p-xylylenediamine, 1,3,5-triaminobenzene, 1,2,4-triaminobenzene, 3,5-diaminobenzoic acid, 3-aminobenzylamine, 4-aminobenzylamine; aliphatic amines such as ethylenediamine, propylenediamine; alicyclic polyfunctional amines such as 1,2-diaminocyclohexane, 1,4-diaminocyclohexane, 4-aminopiperidine, 4-aminoethylpiperazine; secondary amines such as piperazine, 1,3-bispiperidylpropane, etc. can be mentioned. Among them, in consideration of separation performance, water permeation resistance, and heat resistance, it is preferably an aromatic polyfunctional amine having 2 to 4 of at least one of primary amino groups and secondary amino groups in one molecule. As such a polyfunctional aromatic amine, m-phenylenediamine, p-phenylenediamine, or 1,3,5-triaminobenzene is preferably used. In particular, m-phenylenediamine is more preferably used in view of easy availability and ease of handling. These polyfunctional amines can be used alone or as a mixture of two or more. When mixing two or more polyfunctional amines, the above amines may be combined with each other.

[0056] A polyfunctional acid halide is an acid halide having at least two carbonyl halide groups in one molecule. For example, Examples of trifunctional acid halides include trimesic acid chloride, 1,3,5-cyclohexanetricarboxylic acid trichloride, 1,2,4-cyclobutanetricarboxylic acid trichloride, etc., Examples of the difunctional acid halides include aromatic difunctional acid halides such as biphenyldicarboxylic acid dichloride, azobenzenedicarboxylic acid dichloride, terephthalic acid chloride, isophthalic acid chloride, naphthalenedicarboxylic acid chloride; aliphatic difunctional acid halides such as adipoyl chloride, sebacoyl chloride; and alicyclic difunctional acid halides such as cyclopentanedicarboxylic acid dichloride, cyclohexanedicarboxylic acid dichloride, tetrahydrofuran dicarboxylic acid dichloride. Considering the reactivity with polyfunctional amines, the polyfunctional acid halide is preferably a polyfunctional acid chloride. Further, considering the separation performance and heat resistance of the obtained forward osmosis membrane, the polyfunctional acid chloride is more preferably a polyfunctional aromatic acid chloride having 2 to 4 carbonyl chloride groups in one molecule. In particular, from the viewpoints of easy availability and easy handling, it is preferable to use trimesic acid chloride. These polyfunctional acid halides can be used alone or as a mixture of two or more.

[0057] The usage ratios of the polyfunctional amine and the polyfunctional acid halide may be appropriately set so that the separation active layer exhibits desired separation performance, taking into account the type of the porous support layer, the conditions of interfacial polymerization, etc. Appropriate usage ratios of the polyfunctional amine and the polyfunctional acid halide can be easily determined by a small number of preliminary experiments by those skilled in the art.

[0058] The interfacial polymerization between the polyfunctional amine and the polyfunctional acid halide can be carried out according to a conventional method. The obtained separation active layer may be appropriately subjected to heat treatment. This heat treatment is preferably carried out in a wet state. The heat treatment of the separation active layer may be carried out, for example, with hot water or with high-temperature and high-pressure steam in a pressure kettle such as an autoclave. By subjecting the separation active layer to heat treatment, although the reason is not clear, the reverse diffusion of the induction solution is reduced.

[0059] (Method for producing flat-sheet forward osmosis membrane) In the production of a flat-film forward osmosis membrane having a separation active layer composed of polyamide on one surface of a flat-film porous support layer, first, a flat-film porous support layer is produced. The production of the flat-film porous support layer can be carried out by using a desired resin, for example, by known methods such as melt extrusion molding, solution casting method, calendering method, etc., or by a method with appropriate modifications by those skilled in the art. By forming a separation active layer composed of polyamide on one surface of the flat-film porous support layer thus obtained, a suitable flat-film forward osmosis membrane can be obtained. As a preferred method for forming the separation active layer in the present embodiment, for example, a method of performing interfacial polymerization by bringing a first solution containing a polyfunctional amine and a second solution containing a polyfunctional acid halide into contact with each other in this order on one surface of the porous support layer can be mentioned. Regarding the polyfunctional amine, the solvent of the first solution, the polyfunctional acid halide, the solvent of the second solution, and the conditions for interfacial polymerization, the descriptions in the formation of the separation active layer of the hollow fiber forward osmosis membrane can be respectively referred to. It is also the same as in the case of the hollow fiber forward osmosis membrane that heat treatment may be performed after the formation of the separation active layer.

[0060] In the concentration method of the present invention, when the forward osmosis membrane is used in the form of a forward osmosis membrane module described later, the forward osmosis membrane obtained by performing the above interfacial polymerization on the porous support layer may be modularized, or after modularizing the porous support layer, the above interfacial polymerization is performed on the porous support layer in the module to make the porous support layer in the module a forward osmosis membrane, thereby obtaining a forward osmosis membrane module. Further, the porous support layer may be modularized, the forward osmosis membrane module obtained by performing the above interfacial polymerization on the porous support layer in the module may be disassembled to take out the forward osmosis membrane, stored in another housing, remodularized, and then used.

[0061] 〈Forward Osmosis Membrane Module〉 In the concentration method of the present invention, it is preferable from the viewpoint of the workability of concentration to use the forward osmosis membrane in the form of a forward osmosis membrane module configured by housing the forward osmosis membrane in an appropriate housing. The forward osmosis membrane module preferably has a structure in which the space inside the housing is divided into an analysis solution flow-through space through which the analysis solution flows and an inducer solution flow-through space through which the inducer solution flows by the forward osmosis membrane. These analysis solution flow-through space and inducer solution flow-through space are fluidly blocked except that substances can pass back and forth through the forward osmosis membrane.

[0062] (Hollow fiber forward osmosis membrane module) When the forward osmosis membrane is in the form of a hollow fiber or a tubular shape, the hollow fiber or tubular forward osmosis membrane is housed in the housing as a single forward osmosis membrane or as a bundle of multiple fibers, and both ends of the forward osmosis membrane are fixed in the housing with an adhesive layer. Further, lids are arranged at both ends of the housing. The shape of the housing is preferably, for example, a cylindrical shape, an elliptical columnar shape, a prismatic shape, etc.

[0063] Fig. 1 shows a schematic cross-sectional view showing an example of the structure of the hollow fiber forward osmosis membrane module used in the concentration method of the present invention. In the forward osmosis membrane module (100) of Fig. 1, a plurality of hollow fiber forward osmosis membranes (120) are housed inside the housing (110). Both ends of the hollow fiber forward osmosis membrane (120) are adhesively fixed to the housing (110) by an adhesive layer (130). A lid (111) provided with liquid inlets and outlets is attached to the end face (131) of the adhesive layer. The analysis solution (a) is passed through the analysis solution flow-through space of the forward osmosis membrane module (100) from the analysis solution inlet of the lid (111) (the left opening in Fig. 1) through the space (140) formed by the end face of the adhesive layer and the inner surface of the lid, passes through the inside of the hollow fiber forward osmosis membrane (120), and is discharged from the analysis solution outlet (the right opening in Fig. 1) to the outside of the forward osmosis membrane module (100) and recovered. On the side of the housing (110), there are an induction solution inlet (112) and an induction solution outlet (113). The induction solution (c) is introduced from the induction solution inlet (112) into the induction solution passage space of the forward osmosis membrane module (100), passes through the outside of the hollow fiber forward osmosis membrane (120), and is discharged from the induction solution outlet (113) to the outside of the forward osmosis membrane module (100). In the forward osmosis membrane module (100) of Fig. 1, the inside of the housing (110) is divided into an analysis solution passage space and an induction solution passage space by the hollow fiber forward osmosis membrane (120) and the adhesive layer (130). The two spaces are fluidly blocked except that substances can pass through each other through the hollow fiber forward osmosis membrane (120).

[0064] (Flat sheet forward osmosis membrane module) When the forward osmosis membrane is in the form of a flat sheet, the forward osmosis membrane module preferably has a structure in which the forward osmosis membrane is housed in a housing of an appropriate shape, and the space inside the housing is divided into an analysis solution passage space through which the analysis solution passes and an induction solution passage space through which the induction solution passes by the forward osmosis membrane. In this case, the housing may have an analysis solution inlet and an analysis solution outlet communicating with the analysis solution passage space, and an induction solution inlet and an induction solution outlet communicating with the induction solution passage space. Fixation of the flat sheet forward osmosis membrane inside the housing may be performed by an adhesive layer formed from an appropriate adhesive. With such a structure, the analysis solution is passed from the analysis solution inlet into the analysis solution passage space of the forward osmosis membrane module, passes through one side surface of the flat sheet forward osmosis membrane, and is discharged and recovered from the analysis solution outlet to the outside of the forward osmosis membrane module. Also, the induction solution is introduced from the induction solution inlet into the induction solution passage space of the forward osmosis membrane module, passes through the surface on the opposite side of the flat sheet forward osmosis membrane, and is discharged from the induction solution outlet to the outside of the forward osmosis membrane module.

[0065] In the flat sheet forward osmosis membrane module, as long as the above configuration can be adopted, the shape of the flat sheet forward osmosis membrane inside the housing is arbitrary. For example, it may be in the shape of a flat plate or a wound body. As a flat-film forward osmosis membrane module, preferably, it is a spiral module configured to house a plurality of flat-film forward osmosis membranes laminated and wound through appropriate spacers in a cylindrical housing. The spiral module is preferable in that the effective surface area of the forward osmosis membrane per unit volume is large.

[0066] (Material of the housing) The material of the housing in the forward osmosis membrane module is selected from the viewpoint of having chemical resistance, pressure resistance, heat resistance, impact resistance, weather resistance, etc., such that various performances are not deteriorated by the analysis solution and the induction solution. As the material of the housing, for example, resins, metals, etc. can be used. From the above viewpoints, the material of the housing is preferably selected from resins such as polypropylene, polysulfone, polyethersulfone, polyvinylidene fluoride, polytetrafluoroethylene, perfluoroalkoxyalkane, ABS resin, fiber-reinforced plastic, vinyl chloride resin, etc.; and metals such as stainless steel, brass, titanium, etc.

[0067] (Material of the adhesive) In the forward osmosis membrane module, as the adhesive constituting the adhesive layer for fixing the forward osmosis membrane and the housing, it is desirable that it has good mechanical strength and heat resistance. As the adhesive, an adhesive resin made of resin can be used. Examples of the adhesive resin include thermosetting epoxy resin, thermosetting urethane resin, ceramic-type adhesive, sealing materials obtained by melting polyethylene, low-melting metals, etc. From the viewpoint of chemical resistance, polyethylene is desirable, and from the viewpoints of heat resistance and handleability, epoxy resin is desirable.

[0068] 〈Concentration method〉 The concentration method of the present invention is a concentration method by the forward osmosis method in which the analysis solution and the induction solution are brought into contact through a forward osmosis membrane, and the analysis solvent in the analysis solution is passed through the forward osmosis membrane and moved into the induction solution for removal. Liquid ​When concentrating, it is not necessary to heat the analysis solution and the induction solution. The concentration temperature can be, for example, -20°C or higher and 50°C or lower, preferably 0°C or higher and 35°C or lower, and typically room temperature is acceptable. When concentrating, it is not necessary to pressurize the analysis solution and the induction solution.

[0069] However, in the first aspect of the present invention, pressurization applied by a liquid feed pump or the like is acceptable for passing the analysis solution and the induction solution. However, from the viewpoint of avoiding adsorption of the analysis solute to the membrane, the applied pressure to the analysis solution is preferably kept below 500 kPa. In the first aspect of the present invention, the analysis solution and the induction solution may each be stationary or moving with respect to the forward osmosis membrane. In order to perform uniform and efficient concentration in a short time, it is preferable to move the analysis solution and the induction solution relative to the forward osmosis membrane surface, and more preferably, to circulate the analysis solution and the induction solution through the forward osmosis membrane surface.

[0070] When the forward osmosis membrane is in the form of hollow fibers, the flow rates of the analysis solution and the induction solution are preferably 0.03 cm / s or more and 15 cm / s or less, respectively, as the linear velocity in the longitudinal direction of the hollow fiber forward osmosis membrane. When the linear velocity is 0.03 cm / s or more, the analysis solution near the forward osmosis membrane can be smoothly updated, and the osmotic pressure difference between the analysis solution and the induction solution passing through the forward osmosis membrane can be maintained high, which is preferable from the viewpoint of improving productivity. On the other hand, when the linear velocity is 15 cm / s or less, the pressure loss of the analysis solution flowing through the inner space of the hollow fiber forward osmosis membrane can be reduced, and the loss of the analyte due to adsorption to the forward osmosis membrane can be suppressed, which is preferable. The flow directions of the analysis solution and the induction solution may be parallel flow or countercurrent flow.

[0071] On the other hand, in the second aspect of the present invention, since the analysis solution is not circulated or passed through, pressurization applied by a liquid feed pump or the like is not required either. The induction solution may be circulated or passed through, but is preferably not circulated or passed through.

[0072] In the second aspect of the present invention, since the analysis solution is not circulated or passed through, the analysis solution does not move relative to the forward osmosis membrane. However, the volume of the analysis solution decreases as concentration progresses. At this time, movement in such a manner that the analysis solution with decreased volume gathers into a small area due to surface tension is allowed. Also, movement in such a manner that an amount of the analysis solution capable of contacting the forward osmosis membrane is arranged and a new separated solution is replenished by the amount of the decreased volume is allowed.

[0073] (Concentrated analysis solution) In this way, a concentrated analysis solution, which is a concentrated analysis solution, is obtained. The concentrated analysis solution obtained by the concentration method of the present invention contains the analysis solute contained in the raw material analysis solution without being denatured or decomposed and has a high recovery rate. According to the concentration method of the present invention, the concentration of the analysis solute contained in the concentrated analysis solution can be 0.02 ppm or more, and further, this value can be 0.04 ppm or more, 0.05 ppm or more, 0.06 ppm or more, 0.08 ppm or more, or 0.10 ppm or more. This value does not need to be excessively high as long as the desired analysis is possible in the analysis performed subsequent to the concentration method of the present invention, and may be, for example, 1 wt% or less.

[0074] Also, the sensitivity improvement rate expressed as the ratio to the concentration of the analysis solute contained in the analysis solution before concentration can be 2.0 or more and less than 2,000 in the first aspect of the present invention, and can be 1.5 or more and less than 2,000 in the second aspect. When the sensitivity improvement rate is 1.5 or more or 2.0 or more, the concentration of the analyte in the concentrated analysis solution becomes sufficiently high, and the sensitivity at the time of the analysis performed subsequent to the concentration is improved, which is preferable. On the other hand, when the sensitivity improvement rate is less than 2,000, an excessive increase in the viscosity of the concentrated analysis solution can be suppressed, and a decrease in the concentration efficiency due to a decrease in the mass diffusion rate of the solution near the forward osmosis membrane can be avoided, which is preferable. Also, when the sensitivity improvement rate is less than 2,000, the concentration time can be shortened, which is preferable. In the concentrated analysis solution obtained by the method of the present invention, the concentration of the analyte is increased, and the sensitivity of the analysis planned after concentration is improved. Therefore, in this specification, instead of the term "concentration magnification", the term "sensitivity improvement rate" is used. This "sensitivity improvement rate" is equal to the above-mentioned "analyte concentration magnification".

[0075] As described above, the sensitivity improvement rate is preferably 2.0 or more and less than 2,000 from the first aspect of the present invention, and preferably 1.5 or more and less than 2,000 from the second aspect. More preferably, it is 2.0 or more and less than 1,000, and still more preferably 5.0 or more and less than 500. The more preferable sensitivity improvement rate varies depending on the type of the analysis solution. The preferable sensitivity improvement rates for each type of the analysis solution are listed as follows. Natural water such as pond water, river water, and seawater, and treated water such as water purification plants and sewage treatment plants: 5.0 times or more and less than 1,000 times Sewage, agricultural water, fishery water for aquaculture, factory wastewater, and cleaning rinse liquid in the manufacturing process: 5.0 times or more and less than 1,000 times Biologically-derived liquids such as blood, urine, tears, and sweat: 2.0 times or more and less than 50 times Process solutions in pharmaceutical manufacturing, cosmetics manufacturing, chemical manufacturing, etc.: 2.0 times or more and less than 500 times

[0076] 《Concentration device》 The concentration method according to the first aspect of the present invention is preferably carried out using a concentration device including, for example, a forward osmosis membrane module including a forward osmosis membrane, an analysis solution tank, an analysis solution feed pipe, an inducing solution tank, and an inducing solution feed pipe. This concentration device may further include an analysis solution feed pump, an inducing solution feed pump, and the like.

[0077] In this concentration device, the "dead volume" defined as the sum of the volume of the analysis solution passage portion of the forward osmosis membrane module and the volume of the analysis solution feed pipe is 500 mL or less. When concentrating the analysis solution, it is difficult to make the volume of the concentrated analysis solution smaller than the dead volume of the concentration device. That is, when the volume of the analysis solution becomes smaller than the dead volume, the liquid volume in the device becomes insufficient and the analysis solution cannot circulate. Therefore, if the dead volume of the concentration device is set to 500 mL or less, the analysis solution can be concentrated up to this volume, and thus a high sensitivity improvement rate can be obtained, which is preferable. The dead volume of the concentration device is 500 mL or less, preferably 300 mL or less, more preferably 100 mL or less, still more preferably 50 mL or less, particularly preferably 30 mL or less, and most preferably 15 mL or less. The dead volume of the concentration device is preferably small, but it is practically impossible to make this value zero (0). Even if the dead volume of the concentration device is 0.02 mL or more, 0.1 mL or more, 0.5 mL or more, 1 mL or more, 3 mL or more, 5 mL or more, or 10 mL or more, the effects of the present invention will not be impaired.

[0078] FIG. 2 shows a schematic diagram showing an example of the structure of a concentration device used in the concentration method according to the first aspect of the present invention. The concentration device (200) in FIG. 2 includes a forward osmosis membrane module (100), an analysis solution tank (210), an analysis solution feed pump (211), an analysis solution feed pipe (212), an inducing solution tank (220), an inducing solution feed pump (221), and an inducing solution feed pipe (222). The analysis solution (a) is stored in the analysis solution tank (210) and is fed to the forward osmosis membrane module (100) by the analysis solution feed pump (211). The analysis solution (a) is fed through the analysis solution feed pipe (212) that connects the analysis solution tank (210) and the analysis solution feed pump (211), the analysis solution feed pump (211) and the forward osmosis membrane module (100), and the forward osmosis membrane module and the analysis solution tank, respectively. The inducing solution (c) is stored in the inducing solution tank (220) and is fed to the forward osmosis membrane module (100) by the inducing solution feed pump (221). The inducing solution (c) is fed through the inducing solution feed pipe (222) that connects the inducing solution tank (220) and the inducing solution feed pump (221), the inducing solution feed pump (221) and the forward osmosis membrane module (100), and the forward osmosis membrane module and the inducing solution tank, respectively.

[0079] The bottom of the analysis solution tank (210) may be conical. If the bottom of the analysis solution tank (210) is conical, even when concentration progresses and the volume of the analysis solution (a) decreases, the analysis solution (a) that has gathered in the conical portion at the bottom of the tank can be fed. Therefore, it is preferable that the bottom of the analysis solution tank (210) is conical in that concentration can be continued until the analysis solution (a) becomes an extremely small amount. The bottom of the inducing solution tank (220) may be conical, similar to the bottom of the analysis solution tank (210). When the bottom of the inducing solution tank (220) is conical, by installing the end of the inducing solution feed pipe (222) near the bottom of the inducing solution tank (220), even when the amount of the inducing solution (c) is small, the inducing solution (c) that has gathered in the conical portion at the bottom of the inducing solution tank (220) can be fed without air bubbles being mixed in, which is preferable. This mode is advantageous in that efficient concentration can be performed even when a small amount of the inducing solution (c) is used during concentration.

[0080] The analysis solution feed pump (211) and the inducing solution feed pump (221) may be appropriately selected in consideration of the type of the analysis solution (a) or the inducing solution (c), the feed flow rate, the scale of the concentration device (200), etc., respectively. As the analysis solution feed pump (211) and the inducing solution feed pump (221), respectively, From the viewpoint of avoiding contact with parts other than the feed pipe, tube pumps, peristaltic pumps, etc. are; From the viewpoint of being able to be composed of a fluorine-based material with less solute adsorption, diaphragm pumps, etc. are; From the perspective of desiring a small size and high workability, a piezoelectric pump, a bimorph pump, etc. are; each preferable.

[0081] The driving power of the analysis solution feeding pump (211) and the induction solution feeding pump (221) is preferably 500 W or less, more preferably 100 W or less, and even more preferably 50 W or less, respectively. By using a small pump with low driving power, the size of the entire concentration device can be reduced, which is preferable from the viewpoints of improving the workability, operability, etc. of concentration. By miniaturizing the concentration device, it becomes possible to arrange a large number of concentration devices in a limited space, and a large number of concentration devices can be operated simultaneously to concentrate a large number of samples.

[0082] The analysis solution feeding pump (211) and the induction solution feeding pump (221) may each be driven by a mobile battery. A concentration device including a pump that can be driven by a mobile battery can be used in a place without a fixed power source, so the concentration of the analysis solution can be performed at an arbitrary location. As places where a concentration device including a mobile battery-driven pump can be used, for example, the sampling site of the analysis solution, inside a cold storage, etc. can be considered. The pump driving part, power supply part, etc. of the analysis solution feeding pump (211) and the induction solution feeding pump (221) may each be covered with a partition wall such as an acrylic plate. The partition wall may be provided with one or more gas introduction parts and one or more gas discharge parts. Then, an inert gas such as nitrogen may flow into the space covered by the partition wall from the gas introduction part and be discharged from the gas discharge part to fill the space covered by the partition wall with the inert gas. At that time, flow rate adjustment means such as a flow meter and a flow controller may be provided to adjust at least one of the introduction rate and the discharge rate of the inert gas. As described above, the surrounding space of the pump driving unit, power supply unit, etc. of the liquid delivery pump can be filled with an inert gas. By filling the surrounding space of the pump driving unit, power supply unit, etc. of the liquid delivery pump with an inert gas, even when a combustible substance such as an organic solvent is used for at least one of the analysis solvent and the induction solvent, oxygen, which is a supporting combustion substance, can be removed from the ignition source, and the risk of explosion can be reduced, which is preferable.

[0083] In addition, in the concentration device (200) of FIG. 2, the total volume of the portion where the analysis solution is disposed or passed through in the forward osmosis membrane module (100) and the volume of the analysis solution delivery pipe (212) is the dead volume.

[0084] 《Concentration Kit》 In the second aspect of the present invention, it is planned to apply it to a small amount of analysis solution with an analysis solution amount Vf of 50 mL or less. Therefore, it is convenient to perform the concentration method according to the second aspect of the present invention using a small-sized concentration kit having a structure capable of bringing the analysis solution and the induction solution into contact with each other through a forward osmosis membrane. The concentration kit applied to the second aspect of the present invention is A concentration kit for performing the concentration method according to the second aspect of the present invention, which has a configuration capable of bringing the analysis solution and the induction solution into contact with each other through a forward osmosis membrane, passing the analysis solvent in the analysis solution through the forward osmosis membrane, and moving it into the induction solution for removal, Liquid does not include a circulation means, and the amount Vf of the analysis solution that can be filled is 0.01 mL or more and 50 mL or less, and is a concentration kit. The forward osmosis membrane used in this concentration kit may be in the form of hollow fibers or tubes, or may be in the form of a flat membrane. When the forward osmosis membrane is in the form of hollow fibers or tubes, the concentration kit applied to the second aspect of the present invention may have a configuration in which an analysis solution-containing forward osmosis membrane with the analysis solution disposed in the inner space of the hollow fiber or tubular forward osmosis membrane can be immersed in the induction solution.

[0085] When the forward osmosis membrane is in the form of hollow fibers or tubes, the concentration kit applied to the second aspect of the present invention may have a configuration in which an analysis solution-containing forward osmosis membrane with the analysis solution disposed in the inner space of the hollow fiber or tubular forward osmosis membrane can be immersed in the induction solution. In the concentration kit of this embodiment, a configuration in which an analytical solution-containing forward osmosis membrane, in which the analytical solution is disposed in the inner space of a hollow fiber-shaped or tubular forward osmosis membrane, can be immersed in an inducing solution can, for example, exemplify the following forms.

[0086] It comprises one or more hollow fiber-shaped or tubular forward osmosis membranes and a container. An analytical solution is disposed in the inner space of the hollow fiber-shaped or tubular forward osmosis membrane to form an analytical solution-containing forward osmosis membrane. A configuration in which the analytical solution-containing forward osmosis membrane can be immersed in the inducing solution by disposing the inducing solution in the container is provided in a concentration kit (first concentration kit). One or more hollow fiber-shaped or tubular forward osmosis membranes are in the form of a forward osmosis membrane module housed in a cylindrical housing. An analytical solution is disposed in the inner space of the hollow fiber-shaped or tubular forward osmosis membrane to form an analytical solution-containing forward osmosis membrane. A configuration in which the analytical solution-containing forward osmosis membrane can be immersed in the inducing solution by disposing the inducing solution in the inner space of the housing and the outer space of the analytical solution-containing forward osmosis membrane is provided in a concentration kit (second concentration kit). etc.

[0087] In the first concentration kit, the number of hollow fiber-shaped or tubular forward osmosis membranes is preferably set such that the ratio of the volume Vf of the analytical solution applied to the first concentration kit to the total M of the effective membrane areas of the forward osmosis membranes becomes a predetermined value. Examples of the container for disposing the inducing solution include a petri dish and the like. The amount of the inducing solution is preferably about 0.2 times or more and 100 times or less the amount of the analytical solution. The amount of the induction solution is preferably an amount capable of immersing at least a part of the forward osmosis membrane containing the analysis solution. In this case, it is preferable that the vicinity of the center in the longitudinal direction of the forward osmosis membrane containing the analysis solution is immersed in the induction solution, and both ends of the forward osmosis membrane containing the analysis solution are not immersed in the induction solution and are disposed outside the induction solution, and it is preferable that both ends of the forward osmosis membrane containing the analysis solution are held at a position higher than the vicinity of the center immersed in the induction solution. According to such an embodiment, when the analysis solution in the portion immersed in the induction solution is concentrated and the volume decreases, the analysis solution in the portion not immersed in the induction solution is sequentially replenished and moves to a position where it can be concentrated.

[0088] Alternatively, a tube or a syringe may be connected to one end of the hollow fiber-shaped or tubular forward osmosis membrane to hold a solution that cannot fit into the inner space of the forward osmosis membrane. In this case, when the analysis solution in the inner space of the forward osmosis membrane is concentrated and the volume decreases, the analysis solution held in the tube or syringe is replenished into the inner space of the forward osmosis membrane and moves to a position where it can be concentrated. Furthermore, after disposing the analysis solution in the inner space of the hollow fiber-shaped or tubular forward osmosis membrane, sealing the end portion not connected to the tube or syringe is also a preferred embodiment. In this embodiment, the analysis solution in the tube or syringe is sequentially replenished only by the amount of the volume decreased due to the concentration of the analysis solution. Therefore, by tracking the decreased amount of the analysis solution in the tube or syringe, the degree of concentration of the analysis solution can be known. The tracking of the decreased amount of the analysis solution in the tube or syringe can be performed, for example, by reading a scale previously attached to the tube or syringe.

[0089] The filling of the analysis solution into the inner space of the hollow fiber-shaped or tubular forward osmosis membrane, or the recovery of the concentrated analysis solution from the forward osmosis membrane containing the analysis solution after concentration, or both of these may be performed, for example, by a syringe. An embodiment in which the hollow fiber-shaped or tubular forward osmosis membrane and the syringe are previously connected via an appropriate tube as necessary is also preferable.

[0090] The number of hollow fiber or tubular forward osmosis membranes in the second concentration kit is the same as that in the first concentration kit. In the second concentration kit, in order to hold the induction solution in the inner space of the housing and the outer space of the forward osmosis membrane containing the analysis solution, both ends of the forward osmosis membrane may be fixed in the housing with an adhesive layer. With this configuration, the space in the housing can be divided into an analysis solution placement space where the analysis solution is placed and an induction solution placement space where the induction solution is placed by the forward osmosis membrane. In this case, the housing may have one or more holes for filling and discharging the induction solution. For example, the housing may have two holes, one hole being for filling and discharging the induction solution, and the other hole being for the entry and exit of air during filling and discharging of the induction solution. As the concentration of the analysis solution progresses, the amount of the induction solution increases, so by tracking the amount of the induction solution, the degree of concentration of the analysis solution can be known. Examples of the method for tracking the amount of the induction solution include a method of quantifying the amount of the induction solution discharged outside the housing.

[0091] Also, in the second concentration kit, a mode in which a tube is connected to one end or both ends of the forward osmosis membrane and the open end of the tube is held at a position higher than the end of the forward osmosis membrane is also suitable. In this case, an excess amount of the analysis solution may be placed in the tube. According to such a mode, when the analysis solution in the housing is concentrated and its volume decreases, the analysis solution in the transparent tube is sequentially replenished into the housing and moves to a position where it can be concentrated. Also, by tracking this replenishment amount, the degree of concentration of the analysis solution can be known.

[0092] When the forward osmosis membrane is in a flat membrane shape, the concentration kit applied to the second aspect of the present invention is having one or more partition structures for storing the analysis solution on one side of the flat membrane-shaped forward osmosis membrane, the analysis solution stored in the partition structure can be in contact with one side of the flat membrane-shaped forward osmosis membrane, and a concentration kit (third concentration kit) having a configuration in which the induction solution can be in contact with the other side of the flat membrane-shaped forward osmosis membrane.

[0093] The volume of each partition is preferably 0.01 mL or more and 50 mL or less, more preferably 0.02 mL or more and 40 mL or less, still more preferably 0.05 mL or more and 30 mL or less, particularly preferably 0.10 mL or more and 20 mL or less, and may be 0.15 mL or more and 15 mL or less, or 0.20 mL or more and 10 mL or less. The number of partitions in the third concentration kit is preferably, for example, 1 or more and 100 or less, and may be 1 or more and 50 or less, 1 or more and 30 or less, 1 or more and 20 or less, or 1 or more and 10 or less. The amount of the induction solution is preferably about 0.2 times or more and 1,000 times or less the total amount of the analysis solution to be concentrated. When the third concentration kit has a plurality of partition structures, the same type of analysis solution may be placed in each partition for concentration, or different types of analysis solutions may be placed to concentrate a plurality of types of analysis solutions simultaneously. This third concentration kit may be, for example, a combination of a resin plate having a partition structure and a vat of an appropriate size. Also, a commercially available cell culture set may be applied to constitute the third concentration kit.

[0094] 〈Analysis method〉 According to another aspect of the present invention, there is provided an analysis method in which an analysis solution containing an analysis solute and an analysis solvent is concentrated by the concentration method of the present invention and then subjected to instrumental analysis. The instrumental analysis in the analysis method of the present invention may be, for example, one or more types of analysis selected from the group consisting of liquid chromatography, gas chromatography, inductively coupled plasma analysis, atomic absorption analysis, and ion chromatography. Examples of liquid chromatography include liquid chromatography-mass spectrometry (LC / MS), high performance liquid chromatography (HPLC), etc.; examples of gas chromatography include gas chromatography-mass spectrometry (GC / MS), etc.; examples of inductively coupled plasma analysis include high frequency inductively coupled plasma optical emission spectrometry (ICP-OES / ICP-AES), inductively coupled plasma mass spectrometry (ICP-MS), etc.; respectively.

[0095] The analyzer used in the analysis method of the present invention is preferably small and portable. If the analyzer is portable, it can be used in places without a fixed power source, which is preferable in that the analysis method of the present invention can be implemented at the sampling site of the analysis solution.

Examples

[0096] Hereinafter, the present invention will be specifically described based on examples, but the present invention is not limited by the following examples.

[0097] <Measurement methods for each physical property> First, the measurement methods and calculation methods for each physical property will be described. (1) Osmotic pressure of the induction solution Using the van't Hoff equation shown in the above formula (1), the osmotic pressure of each induction solution was calculated.

[0098] (2) Theoretical concentration ratio The theoretical concentration ratio was calculated according to the following formula. Theoretical concentration ratio (times) = volume of the analysis solution / volume of the concentrated analysis solution

[0099] (3) Sensitivity improvement rate (analysis solute concentration ratio) The sensitivity improvement rate was calculated according to the following formula based on the concentrations of the analysis solutes measured by LC / MS for the analysis solutions before and after concentration, and evaluated according to the following criteria. Sensitivity improvement rate (times) = concentration of the analysis solute in the concentrated analysis solution / concentration of the analysis solute in the analysis solution A: When the sensitivity improvement rate is 8 times or more B: When the sensitivity improvement rate is 6 times or more and less than 8 times C: When the sensitivity improvement rate is 4 times or more and less than 6 times D: When the sensitivity improvement rate is 2 times or more and less than 4 times E: When the sensitivity improvement rate is less than 2 times F: When concentration could not be achieved up to 10 times the theoretical concentration ratio

[0100] 《Reference Examples 1 to 10 and Reference Comparative Examples 1 to 4》 《Reference Example 1》 (1) Production of a hollow fiber forward osmosis membrane module (1-1) Production of a hollow fiber support layer module Polyethersulfone (PES: manufactured by BASF, trade name "Ultrason") was dissolved in N-methyl-2-pyrrolidone (manufactured by Wako Pure Chemical Industries, Ltd.) to prepare a 20% by mass hollow fiber spinning dope. The above dope was discharged from the outer spinneret of a wet hollow fiber spinning machine equipped with a double spinneret, and a mixture of water:triethylene glycol = 50:50 (weight ratio) was discharged from the inner spinneret, and each was extruded into a coagulation bath filled with water to form hollow fibers by phase separation. The obtained hollow fibers were wound onto a winder. The outer diameter of the obtained hollow fibers was 1.0 mm, the inner diameter was 0.7 mm, and the pore diameter of the inner surface was 0.05 μm. These hollow fibers were used as the hollow fiber support layer. The above hollow fiber support layer was cut into 20 cm lengths, and 130 of them were filled into a cylindrical plastic housing with a diameter of 2 cm and a length of 10 cm, and both ends were fixed with an adhesive layer, thereby producing a hollow fiber support layer module with an effective membrane inner surface area of 0.023 m 2 .

[0101] (1-2) Formation of the separation active layer (production of a hollow fiber forward osmosis membrane module) 10 g of m-phenylenediamine and 0.8 g of sodium lauryl sulfate were placed in a 1 L container, and 489.2 g of pure water was further added and dissolved to prepare 0.5 kg of a first solution for interfacial polycondensation. 0.8 g of trimesoyl chloride was placed in another 1 L container, and 399.2 g of n-hexane was added and dissolved to prepare 0.4 kg of a second solution for interfacial polycondensation. The first solution was filled into the core side (inside of the hollow fibers) of the above hollow fiber support layer module, allowed to stand for 5 minutes, and then the liquid was drained to form a thin liquid film of the first solution on the inside of the hollow fiber support layer. Next, the core side pressure was set to atmospheric pressure, and the shell side pressure was set to a reduced pressure of 10 kPa as the absolute pressure. After standing in this state for 5 minutes, while maintaining this pressure, the second solution was fed to the core side at a flow rate of 130 mL / min for 3 minutes to perform interfacial polycondensation. The interfacial polycondensation temperature was 25°C. Next, the hollow fiber support layer module was left standing in a thermostatic bath set at 50°C for 5 minutes to vaporize and remove n-hexane. Further, by washing both the shell side and the core side with pure water, a hollow fiber forward osmosis membrane having a separation active layer made of polyamide on the inner surface of the hollow fiber support layer made of polyethersulfone was housed, and a hollow fiber forward osmosis membrane module was produced. In the obtained hollow fiber forward osmosis membrane module, the total volume Vx (cm 3 ) of two spaces formed by the end face of the adhesive layer and the inner surface of the lid, and the internal volume Vy (cm 3 ) of the hollow fiber membrane, the ratio Vx / Vy was 0.52, and the volume Vm of the portion through which the analysis solution flowed in the hollow fiber forward osmosis membrane module was 0.005 (L).

[0102] (2) Concentration The hollow fiber forward osmosis membrane module obtained above was incorporated into a concentration device having the configuration shown in FIG. 2 to concentrate the analysis solution and analyze the concentrated analysis solution. Using 200 mL of a 10 ppm L-phenylalanine aqueous solution prepared with L-phenylalanine (manufactured by Tokyo Chemical Industry Co., Ltd.) and ion-exchanged water as the analysis solution, and using 1,000 mL of a 10 mass% MgCl 2 aqueous solution prepared with magnesium chloride hexahydrate and ion-exchanged water as the inducing solution. The analysis solution was flowed inside the hollow fiber at a linear velocity of 3.4 cm / s, and the inducing solution was flowed outside the hollow fiber at a linear velocity of 2.0 cm / s to concentrate the analysis solution. The concentration temperature was 25°C. The concentration operation was carried out until the theoretical concentration ratio reached 10 times to obtain a concentrated analysis solution, and the osmotic pressure of the inducing solution and the sensitivity improvement rate were calculated by the above method. The evaluation results are summarized in Table 1.

[0103] 《Reference Example 2》 In Reference Example 2, concentration and evaluation were carried out in the same manner as in Reference Example 1, except that a 10 ppm methanol solution of L-phenylalanine was used as the analysis solution and a 10 mass% methanol solution prepared with anhydrous magnesium chloride and methanol was used as the inducing solution. The evaluation results are summarized in Table 1.

[0104] Example 3 for Reference In Example 3 for Reference, in the interfacial polycondensation for producing the hollow fiber forward osmosis membrane, a solution prepared by using 2.5 g of m-phenylenediamine, 0.8 g of sodium lauryl sulfate, and 496.7 g of pure water as the first solution was used. Otherwise, a hollow fiber forward osmosis membrane module was produced and concentrated and evaluated in the same manner as in Example 1 for Reference. The evaluation results were summarized in Table 1.

[0105] Example 4 for Reference In Example 4 for Reference, concentration and evaluation were performed in the same manner as in Example 1 for Reference, except that the amount Vf of the analysis solution was set to 8.00 L. The evaluation results were summarized in Table 1.

[0106] Example 5 for Reference In Example 5 for Reference, when producing the hollow fiber support layer module, a hollow fiber forward osmosis membrane module was produced in the same manner as in Example 1 for Reference, except that the number of hollow fiber support layers housed in the housing was changed to 26. Concentration and evaluation were performed in the same manner as in Example 4 for Reference. The evaluation results were summarized in Table 1.

[0107] Example 6 for Reference (1) Production of Flat Membrane Forward Osmosis Membrane Module A flat membrane made of polysulfone (manufactured by Sepro Membrane, trade name "PS30", 210 mm × 297 mm, thickness 190 μm) was immersed in the first solution prepared in the same manner as in Example 1 for Reference. Then, excess droplets on the surface of the flat membrane were removed to form a thin liquid film of the first solution on the surface of the flat membrane. Next, the second solution prepared in the same manner as in Example 1 for Reference was poured onto one side of the flat membrane and allowed to stand for 30 seconds to perform interfacial polycondensation. The interfacial polycondensation temperature was set to 25°C. After removing the second solution from the membrane after interfacial polycondensation, it was allowed to stand in a thermostatic bath set at 50°C for 5 minutes to vaporize and remove n-hexane. Further, by washing both sides of the membrane with pure water, a flat membrane forward osmosis membrane having a separation active layer made of polyamide on one side of the flat membrane made of polysulfone was produced. The central part of the obtained flat sheet forward osmosis membrane was cut out to 92 mm × 46 mm and set in an acrylic cell, "CF042D-FO" manufactured by Sterlitech to produce a flat sheet forward osmosis membrane module. The effective membrane area of the flat sheet forward osmosis membrane in this module was 42 cm 2 It was. In this module, the analysis solution had a configuration of flowing through the space on the separation active layer side of the forward osmosis membrane, and the volume Vm of the space through which the analysis solution flowed was 0.017 (L).

[0108] (2) Concentration The flat sheet forward osmosis membrane module obtained above was incorporated into a concentration device having the configuration shown in Fig. 2, and 2.1 L of a 10 ppm aqueous L-phenylalanine solution was used as the analysis solution. The analysis solution and the inducing solution were each flowed at a flow rate of 200 mL / min (4.76 mL / (min×cm per unit effective membrane area of the forward osmosis membrane 2 )) under the condition of countercurrent flow, and concentration was carried out and evaluation was performed. The concentration temperature was 25°C.

[0109] 《Reference Example 7》 In Reference Example 7, a hollow fiber forward osmosis membrane module was produced and concentrated and evaluated in the same manner as in Reference Example 1, except that 10 g of 1,6-diaminohexane was used as the first solution instead of 10 g of m-phenylenediamine during the interfacial polycondensation for producing the hollow fiber forward osmosis membrane. The evaluation results are summarized in Table 1.

[0110] 《Reference Comparative Example 1》 In Reference Comparative Example 1, a hollow fiber forward osmosis membrane module was produced and concentrated and evaluated in the same manner as in Reference Example 1, except that a solution prepared using 1.0 g of m-phenylenediamine, 2.5 g of sodium lauryl sulfate, and 496.5 g of pure water was used as the first solution during the interfacial polycondensation for producing the hollow fiber forward osmosis membrane. The evaluation results are summarized in Table 1.

[0111] 《Reference Comparative Example 2》 In Reference Comparative Example 2, in Reference Example 1, as the inducing solution, 10 mass% MgCl 2Instead of 1,000 mL of the aqueous solution, 1 mass% MgCl 2 Concentration and evaluation were carried out in the same manner as in Reference Example 1, except that 1,000 mL of the aqueous solution was used. The evaluation results are summarized in Table 1.

[0112] 《Reference Comparative Examples 3 and 4》 In these reference comparative examples, concentration and evaluation were carried out in the same manner as in Reference Example 1, except that the amount Vf of the analysis solution was made as described in Table 1 respectively. The evaluation results are summarized in Table 1.

[0113] 《Reference Examples 8 to 10》 In these reference examples, by changing the shape and size of the lid used for the hollow fiber forward osmosis membrane module, the total volume Vx (cm 3 ) of two spaces formed by the end face of the adhesive layer and the inner surface of the lid was changed, and the ratio Vx / Vy to the internal volume Vy (cm 3 ) of the hollow fiber membrane was adjusted as described in Table 2 respectively. Except for this, a hollow fiber forward osmosis membrane module was manufactured and concentrated and evaluated in the same manner as in Reference Example 1. The evaluation results of the sensitivity improvement rate were summarized in Table 2 together with the results of Reference Example 1.

[0114]

Table 1

[0115]

Table 2

[0116] "L-Phe" in Table 1 indicates L-phenylalanine.

[0117] 《Examples A-1 to A-3 and Comparative Example a-1》 In Examples A-1 to A-3 and Comparative Example a-1, as a representative example of a low-molecular-weight medicine, concentration of an aqueous solution containing mizoribine (1-(β-D-ribofuranosyl)-5-hydroxyimidazole-4-carboxamide) was carried out. In Example A-1, a model solution prepared from the reagent Mizoribine was used as the analysis solution. In Example A-2, "Washing Rinse Solution A", which is the washing water after washing a part of the reaction vessel after the Mizoribine synthesis reaction in the commercial-scale Mizoribine production process, was used as the analysis solution. In Example A-3 and Comparative Example a-1, "Washing Rinse Solution B", which is the washing water after washing another part of the reaction vessel after the above-mentioned Mizoribine synthesis reaction, was used as the analysis solution, respectively.

[0118] For the analysis solutions before and after concentration in Examples A-1 to A-3, the following analysis condition X was adopted for HPLC analysis, and for the analysis solution after concentration by an evaporator in Comparative Example a-1, the following analysis condition Y was adopted for analysis, respectively.

[0119] 〈Before concentration: Analysis condition X〉 Column: ACQUITY UPLC HSS T3 1.8μm (inner diameter 2.1mm × 100mm) manufactured by Waters Column temperature: 40°C Sample injection volume: 10 μL Mobile phase: 0.1 mass% phosphoric acid aqueous solution Flow rate: 0.2 mL / min Detector: Diode array detector (190 - 400 nm) Detection wavelength: 280 nm

[0120] 〈After concentration: Analysis condition Y〉 Column: TSKgel ODS-100V (inner diameter 4.6mm × 250mm) manufactured by Tosoh Corporation Column temperature: 40°C Sample injection volume: 20 μL Mobile phase: 0.1 mass% phosphoric acid aqueous solution / acetonitrile mixed solution (volume ratio 90 / 10) Flow rate: 0.8 mL / min Detector: Diode array detector (190 - 400 nm) Detection wavelength: 280 nm

[0121] Quantification of the mizoribine concentration in the measurement under analysis condition X was performed using a calibration curve prepared by subjecting aqueous mizoribine solutions with concentrations of 0 ppm, 0.01 ppm, 0.02 ppm, 0.05 ppm, 0.1 ppm, and 0.2 ppm, which were prepared using reagent mizoribine, to HPLC. Quantification of the mizoribine concentration in the measurement under analysis condition Y was performed using a calibration curve prepared by subjecting aqueous mizoribine solutions with concentrations of 0 ppm, 0.05 ppm, 0.1 ppm, and 0.5 ppm, which were prepared using reagent mizoribine, to HPLC. Taking into account the daily error of the detection sensitivity of HPLC, a calibration curve was created for each measurement day for quantification. Note that for both analysis conditions X and Y, the peak top of the mizoribine peak in the HPLC chart was at an elution time of approximately 3 minutes under analysis condition X and at an elution time of approximately 4 minutes under analysis condition Y.

[0122] ≪Example A-1≫ Using a hollow fiber forward osmosis membrane module and a concentration device similar to those in Reference Example 1, the analysis solution was concentrated and the concentrated analysis solution was analyzed. In this concentration device, the dead volume of the portion through which the analysis solution passed was 15 mL. 1,000 mL of an aqueous mizoribine solution with a concentration of 0.003 ppm, which was prepared using mizoribine (manufactured by Fujifilm Wako Pure Chemical Corporation) and distilled water (manufactured by Fujifilm Wako Pure Chemical Corporation), was used as the analysis solution, and 1,000 mL of a 20 mass% magnesium chloride aqueous solution, which was prepared using magnesium chloride hexahydrate and distilled water, was used as the inducing solution. The analysis solution was flowed inside the hollow fiber at a linear velocity of 2.3 cm / s, and the inducing solution was flowed outside the hollow fiber at a linear velocity of 0.4 cm / s to concentrate the analysis solution. The concentration temperature was set to 25°C. The analysis solution was concentrated to 15 mL, which was equal to the dead volume. After collecting the concentrated solution, 5 mL of distilled water was used to co-wash the inside of the device, and a total of 20 mL of concentrated analysis solution was obtained by combining the co-washing solution. The theoretical concentration ratio was 50 times.

[0123] For the pre-concentration analysis solution and the post-concentration analysis solution, HPLC analysis was performed using an HPLC device, "Nexera" manufactured by Shimadzu Corporation. The analysis conditions were as follows: for both the pre-concentration analysis solution and the post-concentration analysis solution, the above analysis condition X was adopted, and the analysis was carried out with two measurements (n = 2) respectively. The HPLC chart of the pre-concentration analysis solution is shown in Figure 3, and the HPLC chart of the post-concentration analysis solution is shown in Figure 4, together with the calibration curves used for quantification.

[0124] In the HPLC chart of the pre-concentration analysis solution shown in Figure 3, the peak of mizoribine with an elution time of about 3 minutes is not observed, but in the HPLC chart of the post-concentration analysis solution shown in Figure 4, the peak of mizoribine can be confirmed. Using the calibration curve, the concentration of mizoribine in the post-concentration analysis solution calculated from the HPLC chart was 0.113 ppm as the average value of two measurements. The sensitivity improvement rate (analysis solute concentration magnification) calculated from this value and the theoretical value (0.003 ppm) of the mizoribine concentration in the analysis solution before analysis was 37.7 times.

[0125] ≪Reference Example A-2≫ In Reference Example A-2, concentration and evaluation were performed in the same manner as in Example A-1, except that "Washing Rinse Solution A" was used as the analysis solution. For the pre-concentration analysis solution and the post-concentration analysis solution, HPLC analysis was performed with two measurements (n = 2) respectively in the same manner as in Example A-1. The HPLC chart of the pre-concentration analysis solution is shown in Figure 5, and the HPLC chart of the post-concentration analysis solution is shown in Figure 6, together with the calibration curves used for quantification. According to the HPLC analysis, mizoribine was not detected twice (≒0 ppm) from the pre-concentration analysis solution, but mizoribine with an average value of 0.008 ppm was detected twice from the post-concentration analysis solution.

[0126] ≪Example A-3≫ In Example A-3, concentration and evaluation were performed in the same manner as in Example A-1, except that "Washing Rinse Solution B" was used as the analysis solution. For the analysis solution before concentration and the analysis solution after concentration, HPLC analysis was performed twice (n = 2) in the same manner as in Example A-1. The HPLC chart of the analysis solution before concentration is shown in Fig. 7 together with the calibration curve used for quantification, and the HPLC chart of the analysis solution after concentration is shown in Fig. 8. According to HPLC analysis, as the average value of two measurements, the concentration of mizoribine in the analysis solution before concentration was 0.009 ppm, and the concentration of mizoribine in the analysis solution after concentration was 0.197 ppm. The sensitivity improvement rate (analysis solute concentration magnification) calculated from these values was 21.9 times.

[0127] ≪Comparative Example a-1≫ In Comparative Example a-1, 1,000 mL of the same "washing rinse solution B" used in Example A-3 was concentrated to 15 mL using a rotary evaporator. After collecting the concentrated solution, 5 mL of distilled water was used to co-wash the inside of the flask, and a total of 20 mL of the concentrated analysis solution was obtained by combining the co-washing solution. In the concentration step of the evaporator, the water bath was set at 50 °C and concentration was performed under reduced pressure. For the analysis solution after concentration, HPLC analysis was performed twice (n = 2) in the same manner as in Example A-1 except that analysis condition Y was used. The obtained HPLC chart is shown in Fig. 9 together with the calibration curve used for quantification. According to HPLC analysis, the concentration of mizoribine in the analysis solution before concentration was 0.009 ppm as shown in Example A-3, and the concentration of mizoribine in the analysis solution after concentration was 0.021 ppm as the average value of two measurements. The sensitivity improvement rate (analysis solute concentration magnification) was 2.3 times.

[0128] 《Detailed Data of HPLC Analysis》 The quantified values of the mizoribine concentration in the HPLC analysis in Example A-1, Reference Example A-2, Example A-3, and Comparative Example a-1 (each n = 2) are shown in Table 3 below.

[0129]

Table 3

[0130] Examples B-1 to B-7 and Comparative Examples b-1 to b-3 (1) Production of hollow fiber forward osmosis membrane (1-1) Production of hollow fiber support layer As a spinning dope, a homogeneous polymer solution composed of 19% by mass of polysulfone (Udel-P3500, manufactured by Solvay Specialty Polymers), 61% by mass of N-methyl-2-pyrrolidone (manufactured by Fujifilm Wako Pure Chemical Corporation), and 20% by mass of tetraethylene glycol (manufactured by Tokyo Chemical Industry Co., Ltd.) was prepared. The spinning dope was filled into a wet hollow fiber spinning machine equipped with a double spinneret. From the double spinneret, the spinning dope at 40°C and the internal coagulation liquid (water) at 25°C were discharged, and they were made to travel 250 mm in air at a temperature-controlled 30°C and a relative humidity of 98%. Then, it was coagulated in a coagulation bath (external coagulation liquid) filled with water at 30°C, and it was wound up with a free roll as a turn roll at a tension of 20 g to obtain hollow fibers made of polysulfone. The outer diameter of the obtained hollow fibers was 1.02 mm, the inner diameter was 0.62 mm, and the film thickness was 0.20 mm. These hollow fibers were used as the hollow fiber support layer. The above hollow fiber support layer was cut into 30 cm lengths, and 130 of them were filled into a cylindrical plastic housing with a diameter of 2 cm and a length of 25 cm, and both ends were fixed with an adhesive to produce a hollow fiber support layer module.

[0131] (1-2) Formation of separation active layer (production of hollow fiber forward osmosis membrane) 10 g of m-phenylenediamine and 0.8 g of sodium lauryl sulfate were placed in a 1 L container, and 489.2 g of pure water was further added and dissolved to prepare 0.5 kg of the first solution for interfacial polymerization. 0.8 g of trimesoyl chloride was placed in another 1 L container, and 399.2 g of n-hexane was added and dissolved to prepare 0.4 kg of the second solution for interfacial polymerization. The first solution was filled into the core side (inside of the hollow fibers) of the above hollow fiber support layer module, and after standing for 5 minutes, the liquid was drained to form a thin liquid film of the first solution on the inside of the hollow fiber support layer. Next, the core side pressure was set to atmospheric pressure, and the shell side pressure was set to a reduced pressure of 10 kPa as absolute pressure. After leaving it standing for 5 minutes in this state, while maintaining this pressure, the second solution was fed to the core side at a flow rate of 130 mL / min for 3 minutes to conduct interfacial polymerization. The interfacial polymerization temperature was set to 25°C. Next, the hollow fiber support layer module was left standing in a thermostatic bath set at 50°C for 5 minutes to vaporize and remove n-hexane. Further, by washing both the shell side and the core side of the module with pure water, a hollow fiber forward osmosis membrane having a separation active layer made of polyamide on the inner surface of the hollow fiber support layer made of polysulfone was produced.

[0132] This module was disassembled, the hollow fiber forward osmosis membrane was taken out, and it was cut to a length of 20 cm. In the following examples and comparative examples, five obtained hollow fiber forward osmosis membranes were used as a set, and as follows, a small hollow fiber forward osmosis membrane module having the structure shown in FIG. 10 was produced and evaluated. Five hollow fiber forward osmosis membranes were filled in a housing made of an acrylic tube having an inner diameter of 9 mm and an outer diameter of 13 mm, and both ends were fixed with an adhesive so that the effective length of the hollow fiber forward osmosis membrane became 100 mm to produce a small hollow fiber forward osmosis membrane module (the membrane area per forward osmosis membrane was 1.947 cm 2 , and the effective membrane area M per module was 9.73 cm 2 ). The acrylic tube housing was provided with holes at two locations on the tube wall, and a transparent nylon tube having an inner diameter of 2 mm and a length of 400 mm was connected to one of the holes using an adhesive to serve as an induced solution inlet. A scale was attached to this nylon tube so that the increase amount of the induced solution due to the progress of concentration could be traced. The other hole in the housing was made sealable with a cap for air venting when filling the induced solution. Lids were attached to both ends of the acrylic tube housing. The lid has a tube connection part and is designed so that the dead volume is minimized. A tube can be attached to the lid so as to communicate with the inner space of the hollow fiber forward osmosis membrane through the tube connection part.

[0133] (2) Manufacture of flat sheet forward osmosis membrane A flat membrane made of polysulfone (manufactured by Sepro Membrane, trade name "PS30", 210 mm × 297 mm, thickness 190 μm, UF membrane) was immersed in the first solution prepared in the same manner as above. Then, excess liquid droplets on the surface of the flat membrane were removed to form a thin liquid film of the first solution on the surface of the flat membrane. Next, the second solution prepared in the same manner as above was poured onto one side of the flat membrane and allowed to stand for 30 seconds to perform interfacial polymerization. The interfacial polymerization was carried out at room temperature. Furthermore, the membrane after interfacial polymerization was allowed to stand in a thermostatic bath set at 50 °C for 5 minutes to vaporize and remove n-hexane, and then both sides of the membrane were washed with pure water to manufacture a flat sheet forward osmosis membrane having a separation active layer made of polyamide on one side of the flat membrane made of polysulfone. The obtained forward osmosis membrane was cut out into a rectangle of 100 mm × 100 mm and used in the following examples.

[0134] (3) Preparation of analysis solution (3-1) Preparation of low molecular weight dye solution As a model of low molecular weight compounds, Brilliant Blue R (molecular weight 825.97, CAS number 6104-59-2) was used as an aqueous solution with a concentration of 10 ppm for the measurement of the recovery rate in the following examples and comparative examples.

[0135] (3-2) Preparation of analysis solution for concentration As the analyte, L-phenylalanine (manufactured by Tokyo Chemical Industry Co., Ltd.), D-(+)-glucose (manufactured by Tokyo Chemical Industry Co., Ltd.), or L-glutamine (manufactured by Tokyo Chemical Industry Co., Ltd.) was used as an aqueous solution with a concentration of 10 ppm for the evaluation of the sensitivity improvement rate in the following examples and comparative examples.

[0136] (4) Preparation of induction solution As the induction solution in the following examples and comparative examples, an aqueous solution of magnesium chloride (MgCl 2 ) with a concentration of 10 mass% was used.

[0137] Example B-1 (1) Evaluation of low molecular weight dye recovery rate A fluororubber tube with an inner diameter of 4 mm was connected to one end of a small hollow fiber forward osmosis membrane module so as to minimize the dead volume as much as possible, and 1.75 ml of an aqueous brilliant blue R solution was filled into the inner spaces of five hollow fiber forward osmosis membranes. After filling, the opening of the tube was installed at a position higher than that of the small hollow fiber membrane module, and the end face not connected to the tube was sealed to prevent liquid leakage. The solution that could not fit into the inner space of the hollow fiber was retained in the tube. Here, when the amount of the aqueous brilliant blue R solution is Vr (L), the ratio Vr / M of Vr to the effective membrane area M (m 2 ) of the small hollow fiber forward osmosis membrane module was 1.8 L / m 2 . To suppress the volatilization of water in the aqueous brilliant blue R solution during standing, the induction solution inlet and air vent of the small hollow fiber forward osmosis membrane module, and the end face of the tube were sealed. In this state, it was left standing at room temperature for 24 hours. After 24 hours, the aqueous brilliant blue R solution in the inner space of the hollow fiber forward osmosis membrane was recovered, the recovery rate of the solute (brilliant blue R) was measured, and when evaluated according to the following criteria, the evaluation result of the low molecular weight dye recovery rate of Example B-1 was "A". A: When the recovery rate of the solute was 95% or more B: When the recovery rate of the solute was 80% or more and less than 95% C: When the recovery rate of the solute was less than 80%

[0138] (2) Reduction ratio The reduction ratio was calculated according to the following formula. Reduction ratio (times) = volume of the analysis solution / volume of the concentrated analysis solution

[0139] (3) Evaluation of sensitivity improvement rate At both ends of the small hollow fiber forward osmosis membrane module, fluororubber tubes with a length of 80 mm and an inner diameter of 4 mm were respectively connected, and with the open part facing upward, they were fixed with clamps. With this configuration, the liquid that could not enter the inner space of the hollow fiber forward osmosis membrane in the module was stored in the fluororubber tube. As the concentration progressed and the liquid volume in the module decreased, the decreased amount would be replenished into the module. The inner spaces of 5 hollow fiber forward osmosis membranes in the module were filled with 1.0 mL of an aqueous solution of L - phenylalanine as the analysis solution. On the other hand, the air vent hole of the small hollow fiber forward osmosis membrane module was opened, and after filling the induction solution from the induction solution inlet, the air vent hole was sealed. During the filling of the induction solution, operations were carried out so that no air bubbles entered the module. With this device configuration, the increase in the induction solution accompanying the progress of concentration can be tracked and measured by the graduated nylon tube connected to the induction solution inlet. Since the increase amount of the induction solution is consistent with the decreased volume of the analysis solution, by tracking the increase amount of the induction solution, the volume reduction rate of the analysis solution can be known. In this state, at room temperature, concentration was carried out until the volume reduction rate became 10 times. After concentration, the analysis solution recovered from the inner space of the hollow fiber forward osmosis membrane was measured by liquid chromatography - mass spectrometry (LC / MS). From the solute concentrations in the analysis solution before and after concentration, the sensitivity improvement rate derived from the following mathematical formula was calculated and evaluated according to the following criteria. As a result, the evaluation result of the sensitivity improvement rate of Example B - 1 was "A".

[0140] Sensitivity improvement rate (times) = solute concentration in the analysis solution after concentration / solute concentration in the analysis solution before concentration A: When the sensitivity improvement rate was 8 times or more B: When the sensitivity improvement rate was 6 times or more and less than 8 times C: When the sensitivity improvement rate was 2 times or more and less than 6 times D: When the sensitivity improvement rate was less than 2 times E: When effective concentration could not be achieved Note that this sensitivity improvement rate should ideally match the volume reduction rate. However, during the concentration of the analysis solution, losses of solute can occur due to adhesion of the solute to the membrane, dissipation of the solute through the forward osmosis membrane into the draw solution, etc. In the forward osmosis membrane of Example B-1, during the concentration of the analysis solution, there was little loss of solute, and it showed a sensitivity improvement rate of Evaluation "A".

[0141] 《Examples B-2 and B-3》 The sensitivity improvement rate was evaluated in the same manner as in Example B-1, except that the analysis solutions listed in Table 4 were used instead of the L-phenylalanine aqueous solution as the analysis solution. The evaluation results are shown in Table 4.

[0142] 《Example B-4》 (1) Evaluation of low molecular weight dye recovery rate A circular hole with a diameter of 0.64 cm (area 0.32 cm 2 ) was drilled in an acrylic plate with a thickness of 1 mm, and an acrylic pipe with an outer diameter of 10 mm, an inner diameter of 8 mm, and a length of 70 mm was attached. The obtained acrylic plate with the acrylic pipe was adhered to the separation active layer formation surface of the above-mentioned flat membrane forward osmosis membrane with an adhesive to prepare a flat membrane forward osmosis membrane plate having a space for filling the analysis solution (effective membrane area M = 0.32 cm 2 well). The schematic of the obtained flat membrane forward osmosis membrane plate structure is shown in Fig. 11. An aqueous solution of brilliant blue R was injected into the well of this flat membrane forward osmosis membrane plate at a liquid volume Vr = 0.058 ml (Vr / M = 1.8). In this state, it was left standing at room temperature for 24 hours. After 24 hours, the analysis solution in the inner space of the hollow fiber forward osmosis membrane was recovered and evaluated in the same manner as in Example B-1. As a result, the evaluation of the low molecular weight dye recovery rate of Example B-4 was "A".

[0143] (2) Evaluation of sensitivity improvement rate The flat-film forward osmosis membrane plate prepared in the same manner as described above was placed in a vat containing 50 mL of the inducing solution with the acrylic plate attachment surface facing up, such that the inducing solution was in contact with the internal space of the well through the flat-film forward osmosis membrane. A schematic cross-sectional view of the configuration of the apparatus fabricated here is shown in Fig. 12. Into the well of this flat-film forward osmosis membrane plate, an aqueous solution of L-phenylalanine was injected as the analysis solution at a liquid volume Vr = 0.36 mL, and concentration was performed at room temperature until the volume reduction rate became 10 times. After concentration, the analysis solution recovered from the well was evaluated in the same manner as in Example B-1. As a result, the evaluation result of the sensitivity improvement rate for Example B-4 was "A".

[0144] 《Example B-5》 The injection volume of the analysis solution (aqueous L-phenylalanine solution) into the well was set to 3.0 mL, and the low molecular weight dye recovery rate and the sensitivity improvement rate were evaluated in the same manner as in Example B-4. The evaluation results are shown in Table 4.

[0145] 《Example B-6, and Comparative Examples b-1 and b-2》 The injection volume of the analysis solution (aqueous L-phenylalanine solution) into the inner space of the hollow fiber forward osmosis membrane was changed to the values described in Table 4, and the low molecular weight dye recovery rate and the sensitivity improvement rate were evaluated in the same manner as in Example B-1. In Comparative Example b-1, since the injection solution volume was small, the lid and fluororubber tube at the end of the small hollow fiber forward osmosis membrane module were removed, and each solution was directly injected into the inner space of the hollow fiber forward osmosis membrane using a micropipette. In Comparative Example b-2, since the injection solution volume was large, the fluororubber tubes at both ends of the small hollow fiber forward osmosis membrane module were each connected to a bottle so that the solution that could not fit into the module could be stored in the bottle. The evaluation results are shown in Table 4.

[0146] 《Example B-7》 In the interfacial polymerization for producing the hollow fiber forward osmosis membrane, except that a solution prepared by using 2.5 g of m-phenylenediamine, 0.8 g of sodium lauryl sulfate, and 496.7 g of pure water as the first solution was used, the low molecular weight dye recovery rate and the sensitivity improvement rate were evaluated in the same manner as in Example B-1. The evaluation results are shown in Table 4.

[0147] 《Comparative Example b-3》 (2) Evaluation of the sensitivity improvement rate A syringe equipped with a hydrophilic PVDF syringe filter with an average pore size of 0.22 μm (effective membrane area M = 2.8 cm 2 ) was filled with 5.0 ml of an analytical solution (L-phenylalanine aqueous solution). The syringe was operated to discharge 4.5 mL of the filling solution through the filter. The 0.5 mL of the analytical solution remaining in the syringe was recovered, and when the sensitivity improvement rate was evaluated in the same manner as in Example B-1, the evaluation result of the sensitivity improvement rate of Comparative Example b-3 was "D".

[0148]

Table 4

Explanation of symbols

[0149] 100 Forward osmosis membrane module 110 Housing 111 Lid 112 Inducing solution inlet 113 Inducing solution outlet 120 Hollow fiber forward osmosis membrane 130 Adhesive layer 131 End face of the adhesive layer 140 Space formed by the end face of the adhesive layer and the inner surface of the lid 200 Concentration device 210 Analytical solution tank 211 Analytical solution feed pump 212 Analytical solution feed pipe 220 Inducing solution tank 221 Inducing solution feed pump 222 Inducing solution feed pipe a Analytical solution b Concentrated analytical solution c Inducing solution

Claims

1. A concentration method for concentrating an analysis solution containing an analysis solute and an analysis solvent before analysis by an analysis device, comprising: The concentration method is as follows: Using a concentration device including a forward osmosis membrane module including a forward osmosis membrane, an analysis solution tank, an analysis solution delivery pipe, an inducing solution tank, and an inducing solution delivery pipe, A concentration method by forward osmosis, in which the analysis solution and the inducing solution are brought into contact through a forward osmosis membrane, and the analysis solvent in the analysis solution is passed through the forward osmosis membrane and moved into the inducing solution for removal, The total volume of the analysis solution passage part of the forward osmosis membrane module and the volume of the analysis solution delivery pipe is 500 mL or less, The concentration of the analysis solute in the analysis solution is 0.01 ppm or less, and the concentration of the analysis solute in the concentrated analysis solution is 0.02 ppm or more, Concentration method.

2. The effective membrane area M of the forward osmosis membrane is 0.1 cm ２ or more and 0.20 m ２ or less. The concentration method according to claim 1.

3. A concentration method for concentrating an analysis solution containing an analysis solute and an analysis solvent before analysis by an analysis device, comprising: The concentration method is a concentration method by forward osmosis, in which the analysis solution and the inducing solution are brought into contact through a forward osmosis membrane, and the analysis solvent in the analysis solution is passed through the forward osmosis membrane and moved into the inducing solution for removal, The analysis solution is not circulated during concentration, The amount Vf of the analysis solution used in the concentration method is 0.01 mL or more and 50 mL or less, and When an aqueous solution of brilliant blue R with a concentration of 10 ppm, Vr (L), is brought into contact with the forward osmosis membrane having an effective membrane area of M (m2) under the condition of Vr / M = 1.8 L / m2 and left standing at room temperature (25°C) for 24 hours, the amount of brilliant blue R contained in the recovered aqueous solution of brilliant blue R is 80% or more of the amount of brilliant blue R contained in the aqueous solution of brilliant blue R before contact with the forward osmosis membrane, Concentration method.

4. The ratio (Vf / M) of the amount Vf (L) of the analysis solution to the effective membrane area M (m ２ 2) is 0.01 L / m ２ or more and less than 200 L / m ２ 2. The concentration method according to claim 3, wherein

5. The effective membrane area M of the forward osmosis membrane is 0.001 cm ２ or more and 500 cm ２ or less. The concentration method according to claim 3.

6. The concentration method according to claim 3, wherein the viscosity of the analysis solution is less than 5,000 mPa·sec.

7. The concentration method according to claim 3, wherein the amount of brilliant blue R contained in the recovered aqueous solution of brilliant blue R is 90% or more of the amount of brilliant blue R contained in the aqueous solution of brilliant blue R before contact with the forward osmosis membrane.

8. The concentration method according to any one of claims 1 to 7, wherein the forward osmosis membrane comprises one or more selected from the group consisting of polyethersulfone, polysulfone, polyketone, polyetheretherketone, polyphenylene ether, polyvinylidene fluoride, polyacrylonitrile, polyethylene, polyimine, polyimide, polybenzoxazole, polybenzimidazole, sulfonated tetrafluoroethylene, cellulose acetate, and polyamide.

9. The concentration method according to any one of claims 1 to 7, wherein the forward osmosis membrane is a composite membrane comprising a porous support layer and a separation active layer on one or both sides of the porous support layer.

10. The concentration method according to claim 9, wherein the porosity of the porous support layer is 30% or more.

11. The concentration method according to claim 9, wherein the separation active layer is a layer containing polyamide.

12. The concentration method according to any one of claims 1 to 7, wherein the forward osmosis membrane is in a hollow fiber shape, a tubular shape, or a flat membrane shape.

13. The concentration method according to claim 12, wherein the inner diameter of the hollow fiber-shaped or tubular forward osmosis membrane is 20 μm or more and 5,000 μm or less.

14. The concentration method according to any one of claims 1 to 7, wherein the forward osmosis membrane is in a hollow fiber shape or a tubular shape and has a separation active layer on the inner surface of the hollow fiber-shaped or tubular porous support layer.

15. The concentration method according to claim 14, wherein the analysis solution is passed or disposed in the inner space of the hollow fiber-shaped or tubular forward osmosis membrane, and the induction solution is passed or disposed outside the hollow fiber-shaped or tubular forward osmosis membrane.

16. The concentration method according to any one of claims 1 to 7, wherein the forward osmosis membrane is in a flat membrane shape and has a separation active layer on one side surface of the flat membrane-shaped porous support layer.

17. The concentration method according to claim 16, wherein the analysis solution is passed or disposed on the separation active layer side of the flat membrane-shaped forward osmosis membrane, and the induction solution is passed or disposed on the porous support layer side of the forward osmosis membrane.

18. The concentration method according to any one of claims 1 to 7, wherein the induction solution is a solution containing one or more selected from the group consisting of salts, organic acids, sugars, alcohols, glycols, organic polymers, and organic solvents.

19. The concentration improvement rate, expressed as the ratio of the concentration of the analyte contained in the concentrated analytical solution to the concentration of the analyte contained in the analytical solution before concentration, is 2.0 or more and less than 2,000 times, the concentration method according to claim 1 or 2.

20. The concentration improvement rate, expressed as the ratio of the concentration of the analyte contained in the concentrated analytical solution to the concentration of the analyte contained in the analytical solution before concentration, is 1.5 or more and less than 2,000 times, the concentration method according to any one of claims 3 to 7.

21. An analytical method in which an analytical solution containing an analyte and an analytical solvent is concentrated by the concentration method according to any one of claims 1 to 7 and then subjected to instrumental analysis.

22. The instrumental analysis is selected from the group consisting of liquid chromatography, gas chromatography, inductively coupled plasma analysis, atomic absorption analysis, and ion chromatography, the analytical method according to claim 21.

23. A concentration kit for performing the concentration method according to any one of claims 3 to 7, wherein the concentration kit has a configuration in which the analytical solution and the inducing solution are brought into contact with each other through a forward osmosis membrane, and the analytical solvent in the analytical solution can be removed by passing through the forward osmosis membrane and moving into the inducing solution, the concentration kit does not include a circulation means, and the amount Vf of the analytical solution that can be filled in the concentration kit is 0.01 mL or more and 50 mL or less, Concentration kit.

24. The forward osmosis membrane is in the form of hollow fibers or tubular, and has a configuration in which an analytical solution-containing forward osmosis membrane, in which the analytical solution is disposed in the inner space of the hollow fiber or tubular forward osmosis membrane, can be immersed in the inducing solution. The concentration kit according to claim 23.

25. The forward osmosis membrane is in the form of a flat membrane, and has one or more partition structures for storing the analytical solution on one surface of the flat membrane forward osmosis membrane, the analytical solution stored in the partition structure can be in contact with one surface of the flat membrane forward osmosis membrane, and the inducing solution can be in contact with the other surface of the flat membrane forward osmosis membrane, The concentration kit according to claim 23.

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