WO2016017811A1 - Selective biomaterial adsorption/desorption material - Google Patents

Selective biomaterial adsorption/desorption material Download PDF

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Publication number
WO2016017811A1
WO2016017811A1 PCT/JP2015/071853 JP2015071853W WO2016017811A1 WO 2016017811 A1 WO2016017811 A1 WO 2016017811A1 JP 2015071853 W JP2015071853 W JP 2015071853W WO 2016017811 A1 WO2016017811 A1 WO 2016017811A1
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Prior art keywords
desorption
absorption
mesopores
biological
porous body
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PCT/JP2015/071853
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French (fr)
Japanese (ja)
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森 寛
勝 下山
隆伸 香月
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日本化成株式会社
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Priority to JP2016538468A priority Critical patent/JP6658526B2/en
Publication of WO2016017811A1 publication Critical patent/WO2016017811A1/en

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D15/00Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/02Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
    • B01J20/10Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/28Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q

Definitions

  • the present invention relates to a biological material selective absorption / desorption material for selectively absorbing / desorbing a biological material to be collected from a biological material-containing liquid, and in particular, a peptide from a biological fluid such as blood.
  • the present invention relates to a biological material selective absorption / desorption material for efficiently separating and recovering biological material.
  • the present invention also relates to a method for producing a high-purity peptide and a method for separating a peptide using the biological material selective adsorption / desorption material.
  • peptides in blood have attracted attention as biomarkers for early detection and diagnosis of cancer, hepatitis, and other diseases. Since peptides specific for diseases exist in peptides of disease patients, early detection / diagnosis of diseases such as cancer becomes possible by detecting these peptides.
  • silica having mesopores (referred to as “mesoporous silica” in the present invention) by utilizing the property that peptides selectively enter and adsorb into mesopores of silica. .) Has been proposed as a peptide adsorption / desorption material.
  • Patent Document 1 proposes a method in which a peptide contained in serum or plasma is mixed with a dry powder of mesoporous silica having a honeycomb structure so that the peptide is adsorbed and recovered in mesopores of mesoporous silica. ing. Specifically, first, a mesoporous silica powder is adsorbed in a mesopore of mesoporous silica by stirring the dry powder of mesoporous silica in a liquid sample containing the peptide, and then the peptide is adsorbed by centrifugation. Silica is recovered.
  • the recovered product is washed with water and then treated with an acidic buffer to peel and remove proteins or long-chain peptides adsorbed on the outer surface of the mesoporous silica particles.
  • the peptide (short chain peptide) adsorbed in the mesopores of mesoporous silica is recovered by desorption and elution by treating with a peptide recovery solvent consisting of an aqueous solution containing acetonitrile, and this is analyzed. .
  • the method for separating and recovering peptides using mesoporous silica is an effective method for selectively separating and recovering peptides from blood, but in the future for clinical application, it will be used for automation by analyzers. Further improvements are required.
  • mesoporous silica is used as a dry powder, and this is put into blood as it is and stirred.
  • steps of mixing blood and mesoporous silica washing with water, treatment with an acidic buffer, peptide
  • it is necessary to perform solid-liquid separation operations by stirring and mixing the powder and treatment liquid and centrifuging multiple times, and analyze the method that requires such complicated operations multiple times. It is difficult to automate using an apparatus.
  • mesoporous silica powder has the following drawbacks. (1) Even if mesoporous silica powder is put into the liquid and stirred, sufficient contact efficiency cannot be obtained, and the peptide adsorption efficiency and desorption efficiency are low, so that the treatment takes a long time. (2) Originally, it is difficult to thoroughly wash highly hydrophilic silica in a powder state and to separate into solid and liquid by centrifugation, because of residual components contained in the powder suspension. The analysis results may be affected. (3) The recovery efficiency of mesoporous silica powder by centrifugation is poor, and the recovery loss of peptides is large. The low peptide recovery rate is also a cause of insufficient analysis accuracy. (4) Unrecovered powder becomes a clogging substance or a pollutant, which hinders stable operation of the device.
  • the present invention solves the above-mentioned conventional problems, is a selective absorption / desorption material of biological material for selectively absorbing / desorbing and separating the biological material to be collected from the liquid containing biological material,
  • This is a material for selective absorption and desorption of biological materials that is easy to handle, easy to be automated by an analyzer, and capable of separating and collecting biological materials to be collected efficiently in a short time and with a high recovery rate. It is an object of the present invention to provide a method for producing a high-purity peptide and a method for separating a peptide using a material for selectively absorbing and desorbing a biological substance.
  • the gist of the present invention is as follows.
  • a selective absorption / desorption material for a biological material for selectively absorbing / desorbing a biological material from a liquid containing the biological material, the absorption / desorption material having mesopores A selective absorption / desorption material for a biological material, which is a sheet containing a porous body.
  • the absorption / desorption material is a laminate in which an absorption / desorption layer including a porous body having mesopores and a water-permeable layer are laminated.
  • Selective absorption / desorption material is a laminate in which an absorption / desorption layer including a porous body having mesopores and a water-permeable layer are laminated.
  • a biological material selective absorption / desorption material for selectively absorbing / desorbing a biological material from a liquid containing the biological material, the absorption / desorption material having mesopores A selective absorption / desorption material for biological materials, characterized in that it is a laminate in which an absorption / desorption layer containing a porous body and a water-permeable layer are laminated.
  • a selective absorption / desorption material for a biological material for selectively absorbing / desorbing a biological material from a liquid containing the biological material, the absorption / desorption material having mesopores A selective absorption / desorption material for biological materials, comprising a layer containing a porous body and a binder.
  • the porous body having mesopores includes one or more selected from the group consisting of mesoporous silica, silica gel, and ion exchange resin.
  • Selective absorption / desorption material The material for selectively absorbing and desorbing a biological material according to any one of [2] to [5] and [7] to [10], wherein the water-permeable layer is a woven fabric or a nonwoven fabric.
  • Selective absorption / desorption material for biological materials [17] A container capable of holding a liquid containing the biological material, the container having the absorption / desorption material according to any one of [1] to [16] inside.
  • a biological material purification kit comprising the absorption / desorption material according to any one of [1] to [16] and a container capable of holding a liquid containing the biological material.
  • a method for producing a biological material comprising the step of bringing the selective adsorption / desorption material for biological material according to any one of [1] to [16] into contact with a liquid containing the biological material.
  • a method for separating a biological material comprising the step of bringing the selective absorbing / desorbing material for a biological material according to any one of [1] to [16] into contact with a liquid containing the biological material.
  • the selective absorption / desorption material for biological materials of the present invention has the following effects.
  • the biological material to be collected can be recovered simply by immersing it in a liquid containing biological material and pulling it up. It can be adsorbed to a porous body having mesopores in the adsorption / desorption layer.
  • washing with water and treatments with various treatment liquids can be performed with simple operations, automation by an analyzer is easy.
  • the contact efficiency with a liquid containing a biological substance is high, and the contact efficiency with these liquids is high in the case of treatment with a treatment liquid such as water washing, an acidic buffer solution, and a peptide recovery solvent.
  • the adsorption efficiency and desorption efficiency of the biological material are high, and the biological material can be stably separated and recovered with a high yield. Further, the adsorption speed, desorption speed, washing efficiency, and processing efficiency are high, and the time required for the operation of sucking and desorbing the biological material can be greatly shortened. Furthermore, since the washing efficiency and the processing efficiency are high, it is possible to recover a high-purity biological material with few undesirable residual components, and it is possible to perform an accurate analysis without being affected by impurities.
  • the unrecovered powder becomes a clogging substance or a pollutant so that the apparatus can be operated stably.
  • the problem of obstruction can be solved.
  • FIG. It is a schematic diagram which shows an example of the shape of the selective absorption-desorption material of the biological material of this invention, Comprising: (a), (d), (e) figure is a perspective view, (b), (c) figure is a front view FIG. It is process explanatory drawing which shows an example of the manufacturing method of the selective absorption / desorption material of the biological material of this invention.
  • the biological material selective absorption / desorption material according to the embodiment of the present invention is brought into contact with a liquid containing the biological material, the treatment is brought into contact with water for cleaning, and the biological material other than the biological material to be collected
  • “Wetted process” is a combination of the process of contacting with a treatment liquid to remove and remove unnecessary materials, the process of contacting with a desorption liquid such as a biological material recovery solvent for desorption of a biological material to be collected, etc.
  • a desorption liquid such as a biological material recovery solvent for desorption of a biological material to be collected, etc.
  • unnecessary substances other than the biological material to be collected include proteins or long-chain peptides, etc.
  • the treatment liquid for peeling off unnecessary substances is acidic. Examples include a buffer solution.
  • the biological material selective absorption / desorption material according to the present embodiment includes a form (hereinafter, also referred to as a first embodiment) which is a sheet including a porous body having mesopores.
  • a first embodiment a sheet including a porous body having mesopores.
  • another embodiment of the adsorbing / desorbing material according to the present embodiment may be a laminate in which an adsorbing / desorbing material including a porous body having mesopores and a water-permeable layer are laminated (hereinafter referred to as the first). 2).
  • a layer including a porous body having mesopores and a binder may be included (hereinafter also referred to as a third embodiment).
  • the absorption / desorption material of the present invention is not particularly limited as long as it includes a porous body having mesopores and has a sheet-like structure.
  • a thrombotic material that becomes a blood coagulation factor is not preferable.
  • the overall adsorbent / desorbable material is preferably made of a biocompatible material such as a bioinert material or an antithrombotic material.
  • biocompatible materials such as those in which the contact surface with the biological fluid is made of a thrombotic material or a bioinert material by a surface treatment or the like is selected as a biocompatible material. It can be used as a constituent material of the absorption / desorption material.
  • the adsorbing / desorbing material according to the first embodiment is desired to have the following characteristics or conditions, it is preferable to devise various processing and sheet design for that purpose.
  • the porous material having mesopores selectively absorbs and desorbs biological materials, in order to increase the amount of collected biological materials, the porous materials having mesopores contained in the absorption / desorption material It is preferable that both the surface area and the surface area of the mesopores and the pore volume are large.
  • the particle diameter of the porous body may be reduced, or the absorption / desorption layer may be thinned.
  • the porous body having mesopores preferably has good wettability with the liquid during the liquid contact treatment.
  • each member constituting the absorbent / desorbing material for example, a material constituting the water-permeable layer is subjected to a hydrophilic treatment, or the specific gravity of the absorbent / desorbing material is adjusted so as to be easily immersed in the liquid.
  • the porous body having mesopores contained in the absorption / desorption material may or may not flow during the liquid contact treatment. From the viewpoint of contact efficiency with the liquid, it is preferable that the fluid flows. If the flow is too intense, the particles may be damaged by the collision between the porous bodies having mesopores, and there is a possibility that "powdery" occurs where fine porous powder is generated and dropped. Therefore, the dropped porous powder becomes a clogging factor or a contamination factor of the apparatus, and the recovery rate of the peptide also deteriorates. Therefore, it is preferable to adjust the degree of flow to such an extent that no powder leaks. On the other hand, it is preferable that the porous body does not flow during the liquid contact treatment in order to suppress powder leakage and improve the handleability. In order not to flow, the porous body is preferably fixed with a binder.
  • the liquid containing the biological material to be processed typically includes blood (serum or plasma) which is a biological fluid, but is not limited thereto, for example, a biological fluid present in the living body.
  • blood serum or plasma
  • the liquid discharged from the living body to the outside and all of these processing liquids are included.
  • the treatment liquid is a liquid obtained by treating a biological fluid, and the treatment method is not limited as long as the biological substance can be separated and recovered, and a known method can be applied.
  • the living body is not limited to the human body. Specific examples of biological fluids include, but are not limited to, the following.
  • serous fluid such as pericardial fluid, cerebrospinal fluid (spinal fluid), joint fluid (synovial fluid), aqueous humor ( Aqueous humor), saliva, gastric juice, bile, pancreatic juice, intestinal juice, etc.
  • sweat, tears, runny nose, urine, semen, vaginal fluid, amniotic fluid, milk aqueous humor
  • the biological material to be separated and recovered from the liquid containing the biological material is not particularly limited as long as it is selectively penetrated and adsorbed into the porous body having mesopores, but for early detection and diagnosis of diseases.
  • Biological substances that can be used as biomarkers are preferably, for example, biomarkers derived from nucleic acids, peptides, proteins, lipid metabolites, carbohydrate metabolites, and the like.
  • the nucleic acid include DNA and RNA.
  • the dynamic diameter of the biological material in the liquid is usually 0.3 nm or more, preferably 0.4 nm or more, more preferably 0.5 nm or more, and usually 15 nm or less, preferably 12 nm or less, more preferably 10 nm or less. It is.
  • the biological substance is a peptide
  • a short chain peptide having an amino acid residue length of 10 to 100, preferably 10 to 50 is particularly mentioned.
  • the liquid containing the biological material preferably has a small content of impurities other than the biological material to be separated and recovered, and the impurities can be removed by a known method.
  • impurities such as proteins such as albumin and globulin is small.
  • the porous body having mesopores is not particularly limited as long as it has mesopores and is a porous body.
  • Specific examples include mesoporous silica, silica gel, silica / alumina, ion exchange resin, diatomaceous earth, activated carbon, zeolite, and acid clay.
  • mesoporous silica, silica gel, and ion exchange resin are preferable from the viewpoint of adsorption and desorption of biological substances.
  • the mesopore diameter is usually 2 nm or more, and usually 50 nm or less, preferably 20 nm or less, more preferably 10 nm or less, still more preferably 8 nm or less, and particularly preferably 5 nm or less.
  • the pore diameter of the mesopores is preferably set according to the type of biological material that is the target of separation and recovery. For example, in order to separate and recover peptides, it is usually 1 nm or more, preferably 2 nm or more, more preferably 3 nm or more, usually 15 nm or less, preferably 12 nm or less, more preferably 10 nm or less.
  • a porous body having mesopores may have pores such as macropores that are not included in the mesopores as long as it has mesopores.
  • the porous body having mesopores preferably has only mesopores.
  • the pore diameter of the porous body having mesopores was determined from EP Barrett, LG Joyner, PHHaklenda, J. Amer. Chem. Soc., Vol. 73, 373 (1951 Plot distribution curve calculated by the BJH method described in the above), that is, the differential nitrogen gas adsorption amount ( ⁇ V / ⁇ (logd); V is the nitrogen gas adsorption volume) is plotted against the pore diameter d (nm). Although it can be obtained from the figure, catalog values can be adopted for commercial products.
  • the pore volume per unit weight of the porous body having mesopores (in this specification, the amount represented by “pore volume / weight” is simply referred to as “pore volume”) is usually 0.00. 1 ml / g or more, preferably 0.2 ml / g or more, and usually 1.5 ml / g or less, preferably 1.2 ml / g or less. If the pore volume is less than the above lower limit, the adsorption / desorption performance tends to be inferior, and if the upper limit is exceeded, the pore structure and particles are easily broken by the liquid contact treatment, and the adsorption / desorption selectivity is reduced, or the powder leaks. May occur.
  • the pore volume of the porous body having mesopores can be determined from the amount of nitrogen gas adsorbed at a relative pressure of 0.98 of the adsorption isotherm, but a catalog value can be adopted for a commercial product.
  • the shape of the porous body having mesopores is not particularly limited as long as the porous body can be formed into a sheet (layered) shape, and may be in the form of a crushed shape, a spherical shape, or a monolith or granulated particle. There may be. Moreover, the thing of the honeycomb structure described in patent document 1 may be sufficient. In the case of granulated particles, those having large gaps between primary particles are preferable in terms of contact efficiency with biological fluids and the like.
  • the surface area outside the particle will increase with respect to the total surface area (the total surface area inside the mesopore and the surface area outside the particle).
  • the pore length in the particles is long. It takes time to penetrate and diffuse into the pores, and it takes a long time for absorption / desorption, washing, and collection of biological materials, which is not preferable.
  • the porous body having mesopores has a specific surface area of usually 100 m 2 / g or more, preferably 200 m 2 / g, and usually 1200 m 2 / g or less, preferably 1000 m 2 / g or less.
  • the specific surface area is at least the above lower limit, the target product can be efficiently absorbed and desorbed.
  • the strength of the porous body can be ensured and the durability of the absorbent / desorbable material can be improved.
  • the specific surface area is measured by the BET single point method.
  • the porous body having mesopores may be used after being subjected to a surface treatment such as a hydrophobization treatment in order to prevent substances other than the target substance from adsorbing to the outer surface.
  • a surface treatment such as a hydrophobization treatment
  • the outer surface of a porous body having mesopores is hydrophobized by silicone treatment and trimethylsilylation treatment, and the target biological material is selectively contained only in the pores of the porous body having mesopores. You may modify
  • the absorption / desorption layer may be composed only of a porous body having mesopores, or may be composed of a porous body having mesopores and another material.
  • the material having the mesopores does not significantly impair the absorption / desorption function of biological substances, and more
  • the first embodiment of the present invention includes an aspect in which the material constituting the absorption / desorption layer flows during the liquid contact treatment. In this case, the absorption / desorption layer may or may not include a binder.
  • the binder is not particularly limited as long as a porous body having mesopores can be molded, but a thermoplastic resin is preferably used.
  • the thermoplastic resin is not particularly limited as long as it can mold a porous body having mesopores (for example, adhesion by thermal fusion).
  • the water absorption and MFR described below are satisfied.
  • ethylene vinyl acetate copolymer From the viewpoint of moldability and solvent resistance of the porous body, ethylene vinyl acetate copolymer, saponified ethylene vinyl acetate copolymer, polyester, polyamide, and polyethylene are preferable.
  • ethylene acetic acid has the advantage that the elution of the components is small, the absorption / desorption characteristics of the porous body having mesopores are difficult to deteriorate, and the porous body having mesopores is not easily dropped even if the absorption / desorption material is subjected to external stress.
  • a vinyl copolymer is more preferable.
  • the thermoplastic resin has a water absorption rate of 0.2% or more measured by the following method.
  • a thermoplastic resin having a water absorption rate of less than 0.2% is highly hydrophobic, and in the absorption / desorption layer, the thermoplastic resin exposed in the gaps between the mesoporous silica particles repels water, so that the absorption / desorption material Absorption / desorption performance may be inferior.
  • the higher the water absorption rate of the thermoplastic resin the more preferable, and particularly 0.5% or more is preferable.
  • the upper limit of the water absorption rate of the thermoplastic resin is usually 10% or less.
  • thermoplastic resin Water absorption rate of thermoplastic resin
  • the water absorption rate of the thermoplastic resin is used as an index of hydrophilicity of the thermoplastic resin, but the hydrophilicity of the thermoplastic resin can also be expressed by a water contact angle.
  • the thermoplastic resin is formed into a film by the same method as the film for measuring water absorption described above, and the water contact angle measured by the ⁇ / 2 method with respect to the film surface is 95 ° or less, particularly 85 ° or less. It is preferable.
  • the water absorption rate described above does not necessarily correspond to this water contact angle, and there are thermoplastic resins having a low water absorption rate even if the water contact angle is small, and thermoplastic resins having a large water contact angle even if the water absorption rate is large. .
  • the thermoplastic resin preferably has a small MFR, but if the MFR is too small, the fluidity at the time of heat melting is too small, and it may be difficult to mold a porous body having mesopores. Therefore, the MFR of the thermoplastic resin is preferably 1 to 55 g / 10 min, particularly 5 to 50 g / 10 min.
  • MFR of thermoplastic resin Measured according to JIS K6760 at 190 ° C. and 2.16 kg load.
  • thermoplastic resin Usually, 50 degreeC or more, Preferably it is 80 degreeC or more, and is usually 250 degrees C or less, Preferably it is 150 degrees C or less.
  • the melting point of the thermoplastic resin is less than 50 ° C., there is a problem that the thermoplastic resin is likely to be thermally deformed when used at room temperature. In the case where the water-permeable layer is provided, the water-permeable layer may be thermally deformed.
  • the shape of the thermoplastic resin is not particularly limited, but by using a particulate material, a porous body having mesopores and the thermoplastic resin are mixed and pressed to form a sheet that is an adsorption delayer. Can do.
  • thermoplastic resin particles are used, a suitable particle size exists in relation to the particle size of the porous body having mesopores. If the particle diameter of the thermoplastic resin particles is excessively large relative to the particle diameter of the porous body having mesopores, good voids cannot be formed between the porous bodies having mesopores, and the thermoplastic resin is formed during sheet formation.
  • a porous body having mesopores is buried in the resin particles, and a sufficient absorption / desorption function cannot be exhibited. Even if the particle diameter of the thermoplastic resin particles is excessively small, porous bodies having mesopores are in close contact with each other, and the porosity of the absorption / desorption layer is reduced. Thermoplastic resin particles having an excessively small particle size are difficult to obtain as a commercial product and have the disadvantage of being inferior in uniform mixing with a porous material having mesopores.
  • the average particle diameter itself of the thermoplastic resin particles is arbitrary within the range satisfying the above average particle diameter ratio, but is preferably about 5 to 900 ⁇ m from the viewpoint of easy availability and handleability.
  • the average particle diameter of the thermoplastic resin particles is a value determined by a laser diffraction scattering method (water dispersion wet method).
  • the weight ratio of the thermoplastic resin particles constituting the absorption / desorption layer and the porous body having mesopores is It is preferably 1/4 to 4/1, particularly 1/3 to 3/1. If the thermoplastic resin particles are less than this range, the moldability of the porous body having mesopores is poor and it is difficult to form a sheet-like absorption / desorption layer. When there are more thermoplastic resin particles than this range, the resin melted at the time of molding a porous body having mesopores easily fills the voids between the particles, resulting in a decrease in porosity. Furthermore, if the resin enters or covers the pores of the porous body having mesopores, the absorption / desorption performance decreases, and an absorption / desorption material with excellent absorption / desorption performance can be obtained. Can not.
  • inorganic filler By including an inorganic filler having a specific gravity greater than that of the porous material having mesopores in the absorption / desorption layer, the specific gravity of the absorption / desorption material is increased, and it is easy to sink in biological fluids and other treatment liquids. The wettability with biological fluids and other treatment liquids can be improved.
  • inorganic fillers used for such purposes include metal oxide particles such as zircon (zirconium silicate, specific gravity 4.7), quartz (specific gravity 2.7), alumina (specific gravity 4.0), stainless steel, titanium, and the like.
  • One kind or two or more kinds of metal particles such as an alloy (Ti-6Al-4V) and a cobalt-chromium alloy (Vitalium, Co-Cr-Mo alloy) can be used.
  • an alloy Ti-6Al-4V
  • a cobalt-chromium alloy Vitalium, Co-Cr-Mo alloy
  • the particle size of the inorganic filler is excessively large, the thickness of the absorption / desorption layer will be affected, and the porous body having mesopores will move easily in the water-permeable sheet, leading to powder leakage, and conversely If it is excessively small, it becomes easy to fill the voids of the porous body having mesopores and the absorption / desorption performance may be lowered.
  • a material having the same size as the porous body having mesopores is used. .
  • the inorganic filler is used according to the purpose so that the adsorbent / desorbing material has a desired specific gravity.
  • the total volume is used. Is usually 80% or less, preferably 70% or less of the apparent volume of the adsorption / desorption layer, and is usually 5% or more.
  • the coarse silica particles are protruded from the surface of the water-permeable layer, which will be described later, by incorporating coarse particles of silica in the absorption / desorption layer.
  • the wettability of the adsorbing / desorbing material can be enhanced by using the particles as hydrophilic starting points.
  • the particle diameter of the coarse silica particles may be slightly larger than the thickness of the absorption / desorption layer, and is usually 1.5 to 5 times the thickness of the absorption / desorption layer. In the case where coarse particles of silica are contained in the absorption / desorption layer, if the amount is too small, sufficient wettability improvement effect cannot be obtained.
  • the total volume is usually 80% or less with respect to the apparent volume of the absorption / desorption layer, preferably 70% or less, and usually 5% or more.
  • the volume ratio is usually 80% or less with respect to the apparent volume of the absorption / desorption layer, preferably 70% or less, and usually 5% or more.
  • the absorption / desorption layer preferably has a porosity of 10% or more. If the porosity of the absorption / desorption layer is too small, the penetration efficiency of biological fluids and various treatment liquids into the absorption / desorption layer is poor, and excellent absorption / desorption performance with a porous body having mesopores can be sufficiently obtained. It cannot be performed and the cleaning efficiency is inferior.
  • the porosity is preferably 10% or more and is preferably high to some extent.
  • the porosity of the adsorption / desorption layer is usually 15% or more, preferably 20% or more, more preferably 30% or more, and usually 95% or less, preferably 90% or less, more preferably 85% or less. .
  • the porosity of the adsorption / desorption layer is, for example, a value obtained by the following method in the case of an adsorption / desorption layer composed of a porous body having mesopores and thermoplastic resin particles.
  • the porosity of the absorption / desorption layer refers to the void (however, the fineness of the porous body having mesopores) out of the volume formed between the sheets when a smooth surface sheet is laminated on both sides of the absorption / desorption layer.
  • the volume of the constituent material occupying the absorption / desorption layer determined from the specific gravity of the material constituting the absorption / desorption layer and the weight used, and the appearance of the absorption / desorption layer It is calculated
  • the thickness of the absorption / desorption layer is preferably thin from the viewpoint of the permeability and permeability of the liquid during the liquid contact treatment. Therefore, the thickness of the absorption / desorption layer is preferably 20 times or less, more preferably 10 times or less, and more preferably 5 times or less the average particle diameter of the porous body having mesopores contained in the layer. More preferably it is. Moreover, it is preferable that it is 2 times or more. That is, the thickness is preferably such that about 2 to 5 porous layers having mesopores are formed in the thickness direction of the absorption / desorption layer. For example, the thickness of the absorption / desorption layer is preferably 100 ⁇ m or more, more preferably 200 ⁇ m or more, and preferably 2000 ⁇ m or less, more preferably 1500 ⁇ m or less.
  • the absorption / desorption material according to the embodiment of the present invention may have a water-permeable layer.
  • the water permeable layer is not particularly limited as long as it is a material having excellent hydrophilicity, water permeability, and biocompatibility and satisfying mechanical strength, chemical resistance, etc. required for handling. Or it is preferable to use a nonwoven fabric. Although a commercially available thing can be used as a woven fabric or a nonwoven fabric, It is preferable to use a nonwoven fabric as a water-permeable layer from the point which is especially cheap and can obtain easily the thing by which opening adjustment was carried out.
  • fibers constituting the nonwoven fabric or woven fabric used in the water-permeable layer include polyester fibers such as polyethylene terephthalate and polytrimethylene terephthalate; polyacrylic fibers; polyolefin fibers such as polyethylene and polypropylene; polyamide fibers such as nylon 6 and nylon 66
  • polyester fibers such as polyethylene terephthalate and polytrimethylene terephthalate
  • polyacrylic fibers such as polyethylene and polypropylene
  • polyamide fibers such as nylon 6 and nylon 66
  • Such synthetic fibers those obtained by combining one or more semi-synthetic fibers such as rayon and acetate fibers can be used.
  • semi-synthetic fibers, particularly rayon are preferable because they have high wettability, and are easy to handle when desorbing and desorbing, and polyolefin fibers are preferable because of high recovery of biological materials.
  • Polyester fibers are preferable in that they satisfy a good balance between wettability and biological material recovery.
  • fibers with heat-fusibility as a core-sheath structure special fibers with increased hydrophilicity, such as ultra-fine fibers, irregular fiber cross-sections, grooves and recesses on side surfaces, and fiber porosity
  • surface-treated fibers subjected to hydrophilic coating treatment can also be used.
  • the core-sheath fiber is preferable because it can be easily heat-sealed at the time of cutting when the absorption / desorption material of the present invention described later is produced.
  • the water-permeable layer preferably has a larger opening due to the permeability and permeability of various liquids during the liquid contact treatment, but if it is excessively large, the molding stability of the absorption / desorption layer will be inferior. Further, the thickness of the water-permeable layer is preferably thicker from the viewpoint of securing the strength of the absorbent / desorbing material and ease of heat fusion, and thinner for thinner. The water-permeable layer preferably satisfies the following conditions from the standpoints of the permeability, permeability, various strengths of the absorbent / desorbent, and handleability of various liquids during the liquid contact treatment.
  • the thickness of the water-permeable layer is usually 50 ⁇ m or more, preferably 70 ⁇ m or more, more preferably 100 ⁇ m or more, and usually 1000 ⁇ m or less, preferably 500 ⁇ m or less, more preferably 300 ⁇ m or less.
  • Weight of the water-permeable layer (g / m 2) is 1/10 to 10 times the weight of the porous body having mesopores of adsorption and desorption layer (g / m 2), and in particular 1 / 5-5 times It is preferable to use it as follows.
  • the basis weight is usually 10 g / m 2 or more, preferably 20 g / m 2 or more, more preferably 30 g / m 2 or more, and usually 200 g / m 2 or less, preferably It is 150 g / m 2 or less, more preferably 100 g / m 2 or less.
  • the water-permeable layer has an air permeability measured according to JIS L 1096 6.27.1 A method (Fragile method) of usually 50 cc / cm 2 ⁇ sec or more, preferably 70 cc / cm 2 ⁇ sec or more, Further, it is usually 250 cc / cm 2 ⁇ sec or less, preferably 200 cc / cm 2 ⁇ sec or less.
  • a method Frazier method of usually 50 cc / cm 2 ⁇ sec or more, preferably 70 cc / cm 2 ⁇ sec or more, Further, it is usually 250 cc / cm 2 ⁇ sec or less, preferably 200 cc / cm 2 ⁇ sec or less.
  • the specific surface area of the porous body having mesopores in the absorption / desorption layer with respect to the specific surface area of the water-permeable layer is usually 1000 times or more, preferably 10,000 times or more, and usually 10 million times or less.
  • the specific surface area of the water-permeable layer is the value of the surface area of the yarn (fiber) to be formed when the water-permeable layer is composed of a woven fabric or a non-woven fabric, and the specific surface area of the porous body having mesopores. This is the total value of the surface area outside the particle and the surface area inside the pore, and can be determined by the nitrogen gas BET method.
  • the water-permeable layer is composed of a woven or non-woven fabric
  • the fibers constituting the woven or non-woven fabric are highly hydrophobic and sufficient wettability cannot be obtained, the following hydrophilicity improving treatment is applied. May be.
  • a surface treatment using a plasma such as argon or oxygen is performed on a woven fabric or a non-woven fabric to introduce a hydroxyl group to enhance hydrophilicity.
  • hydrophilic copolymer resin using hydrophilic fibers such as cellulose fiber, rayon fiber, polyvinyl alcohol (PVA) fiber, ethylene vinyl acetate copolymer (EVA) fiber, or hydrophilic monomers such as vinyl acetate and vinyl alcohol A fiber, etc., as a fiber constituting a woven fabric or a nonwoven fabric, alone or in addition to those exemplified above as a fiber constituting a nonwoven fabric or a woven fabric used for a water-permeable sheet, mixed with these fibers, Alternatively, it is used by a method of laminating or forming a sheet using a binder or the like as a short fiber.
  • hydrophilic fibers such as cellulose fiber, rayon fiber, polyvinyl alcohol (PVA) fiber, ethylene vinyl acetate copolymer (EVA) fiber, or hydrophilic monomers such as vinyl acetate and vinyl alcohol A fiber, etc.
  • a treatment for physically or chemically fixing hydrophilic groups such as polyethylene glycol, poly (2-hydroxyethyl methacrylate), poly (acrylamide), and sulfonated segment polyurethane to the surface of the woven or non-woven fabric is performed.
  • the surface of the woven or non-woven fabric is subjected to a silica coating treatment to make it hydrophilic. This silica coating may be performed partially by printing dots or lines on a woven or non-woven fabric.
  • the degree of hydrophilicity of the water-permeable layer is such that when a 1 cm square sheet is immersed in water in a form that floats on the water surface, it is buried in water in a short time.
  • the hydrophilicity is preferably such that it is buried within 1 minute, more preferably within 30 seconds.
  • water droplets of pure water when water droplets of pure water are dropped on the water-permeable layer, water starts to penetrate into the sheet within 10 seconds, preferably within 5 seconds. It should be soaked in water.
  • a perforated sheet for example, punching metal
  • a specific gravity material may be included.
  • the water-permeable layer does not become clogged with contaminants or adhere to an adhesive when the absorbent / desorbent is immersed in the biological fluid. Moreover, it is preferable that it is excellent in hydrophilicity from the surface of the permeability of various liquids at the time of a liquid-contact process, and a permeability.
  • the amount of biological material adsorbed on the water-permeable layer is excessive, and the biological material in the pores of the porous body having mesopores in the absorption / desorption layer It is preferable to adjust the surface state as appropriate because there is a possibility that the amount of adsorbed will be reduced.
  • an antithrombotic material is preferably applied, and examples of the antithrombotic material include heparin-immobilized coating material, urokinase-immobilized coating material, thrombomogerin-immobilized coating material, and segmentation.
  • examples of the antithrombotic material include heparin-immobilized coating material, urokinase-immobilized coating material, thrombomogerin-immobilized coating material, and segmentation.
  • examples include polyurethane coating materials, synthetic biocompatible coating materials, phospholipid adsorption or immobilization coating materials (MPC polymers), and alkylated cellulose coating materials.
  • a silicone material such as polydimetalsiloxane can be used for the aqueous layer or a silicone coating can be passed. It may be applied to the aqueous layer.
  • Fluorine resins such as polyethylene and polyolefins typified by polypropylene and polytetrafluoroethylene can be preferably used as a constituent material of the water-permeable layer and also as a coating material.
  • FIG. 1 is a schematic cross-sectional view showing an example of an embodiment of the adsorption / desorption material of the present invention.
  • FIG. 1A is an example of a preferred embodiment of a sheet including a porous body having mesopores.
  • the absorbent / desorbing material 1 is a sheet-like absorbent / desorbing material in which a porous body 2 having mesopores is bonded to each other with a binder 3.
  • a water-permeable layer 5 is laminated on both surfaces of the desorption layer 4.
  • the absorption / desorption layer 4 and the water-permeable layer 5 are bonded together by a binder 3 included in the absorption / desorption layer 4.
  • the thickness of the absorbent / desorbable material in which the water-permeable layer 5 is laminated on both surfaces of the absorbent / desorbable layer 4 is usually 300 ⁇ m or more, preferably 500 ⁇ m or more, and usually 5000 ⁇ m or less, preferably 4000 ⁇ m or less. Preferably it is 3000 micrometers or less.
  • the absorption / desorption layer 4 is composed of a porous body 2 having mesopores and a binder 3. May be included.
  • the water-permeable layers 5 on both surfaces of the absorption / desorption layer 4 may be made of the same material or different materials in one water-permeable layer and the other water-permeable layer.
  • the absorption / desorption layer 4 may or may not include the binder 3.
  • a sheet-like absorption / desorption layer 4 in which porous bodies 2 having mesopores are bonded to each other with a binder 3 is formed as shown in FIG.
  • the (ai) absorption / desorption layer is a porous molded body having mesopores molded without the binder, and (aii) the absorption / desorption layer is a mesopore.
  • Absorption / desorption layer which is a layer formed by passing a porous body having pores to a water-permeable layer, is formed by sandwiching a porous body having mesopores between water-permeable layers.
  • the adsorbing / desorbing material can be formed into a sheet shape by a mode such as maintaining
  • the absorption / desorption layer is a porous molded body having mesopores molded without containing a binder
  • the molded body compresses and molds a porous body having mesopores. Can be obtained.
  • the absorption / desorption layer does not contain a binder
  • the absorption / desorption layer and the water-permeable layer may be laminated using the same material as the binder described above, and heat fusion is performed by the water-permeable layer containing a material that can be fused. You may wear it.
  • the absorption / desorption layer is likely to be brittle, while the amount of the binder can be reduced, and the liquid containing the biological material can be efficiently brought into contact with the porous body having mesopores. preferable.
  • the absorption / desorption layer is a layer formed by fixing a porous body having mesopores to the aqueous layer
  • a porous body having mesopores may be fixed only to one layer, or a porous body having mesopores may be fixed to both water-permeable layers. It is preferable to fix the porous body having mesopores to both water-permeable layers in that the amount of the porous body having mesopores contained in the adsorbing / desorbing material is easily increased.
  • the fixing method is not limited.
  • a porous body having mesopores and a water-permeable layer may be bonded to the water-permeable layer with a binder and a material that can be fused to the water-permeable layer is used. And may be fused.
  • the fixing position of the two water-permeable layers is not limited, and examples thereof include a method of fixing the peripheral portions of the two water-permeable layers and a method of fixing the two water-permeable layers at a predetermined interval.
  • the fixing method is not limited, and may be, for example, adhesion or heat fusion.
  • the aforementioned binder may be used as an adhesive.
  • the water-permeable layer is preferably made of a material that can be heat-sealed.
  • the fixing position is not limited, but it is preferable to join the peripheral edge of the water-permeable layer in order to prevent powder leakage.
  • the porous body 2 having mesopores is water-permeable. Since it is fixed to the layer, it is preferable in that it is difficult for the powder to leak.
  • the design so that the fluidity of the mesoporous silica particles in the adsorption / desorption layer becomes appropriate while ensuring the permeability and permeability of various liquids during the liquid contact treatment.
  • the absorption / desorption layer 4 includes the binder 3, the porous body 2 having mesopores may fall off from the absorption / desorption layer 4 to cause powder leakage, thereby suppressing the powder leakage. In order to do so, it is preferable to devise a design.
  • the absorption / desorption layer 4 includes the binder 3 and the water-permeable layer 5 is laminated on both surfaces of the absorption / desorption layer 4 particularly suppresses the powder from leaking from the absorption / desorption material 1.
  • This is a preferred embodiment, and is preferred in that it is difficult to inhibit the stable operation of the biological material analyzer.
  • FIG. 1B is an example of a preferred embodiment of an absorbent / desorbing material in which an absorbing / desorbing layer including a porous body having mesopores and a water-permeable layer are laminated.
  • Porous bodies 2 having mesopores are bonded to each other with a binder 3 to form a sheet-like absorption / desorption layer 4, and a water-permeable layer 5 is laminated on one surface of the absorption / desorption layer 4.
  • the absorption / desorption layer 4 and the water-permeable layer 5 are bonded together by a binder 3 included in the absorption / desorption layer 4.
  • the water-permeable layer 5 is laminated on one surface of the absorption / desorption layer 4, that is, the thickness of the absorption / desorption material when one absorption / desorption layer and one water-permeable layer are laminated, Usually, it is 150 ⁇ m or more, preferably 200 ⁇ m or more, and usually 3000 ⁇ m or less, preferably 2000 ⁇ m or less.
  • the absorption / desorption layer may be laminated
  • the thickness of the absorption / desorption material is usually 250 ⁇ m or more, preferably 400 ⁇ m or more, and is usually 5000 ⁇ m or less, preferably 3000 ⁇ m or less, more preferably 2000 ⁇ m or less.
  • the adsorption / desorption layer 4 is composed of a porous body 2 having a mesopore and a binder 3. Further, the adsorption / desorption layer 4 according to the present invention is coarse in the inorganic filler and silica described above. It may contain particles. In the configuration in which the water-permeable layer 5 is laminated on one surface of the absorption / desorption layer 4, the absorption / desorption layer 4 may or may not include the binder 3.
  • a sheet-like absorption / desorption layer 4 in which porous bodies 2 having mesopores are bonded to each other with a binder 3 is formed as shown in FIG.
  • the absorption / desorption layer is a porous molded body having mesopores molded without the binder
  • the absorption / desorption layer is a mesopore
  • the absorbing / desorbing material can be formed into a sheet shape by an embodiment such as a layer formed by passing a porous body having pores to the aqueous layer.
  • the absorption / desorption layer is a porous molded body having mesopores molded without containing a binder
  • the molded body is formed by, for example, tableting a porous body having mesopores. It is obtained with.
  • the same material as the binder described above may be used for the lamination of the absorption / desorption layer and the water-permeable layer. May be.
  • the absorption / desorption layer tends to be brittle, while the amount of the binder can be reduced, and the liquid containing the biological material can be efficiently brought into contact with the porous body having mesopores. preferable.
  • the fixing method is not limited.
  • a porous body having mesopores The porous body having mesopores and the water-permeable layer may be fused using a material that can be adhered to the water-permeable layer with a binder and can be fused to the water-permeable layer.
  • the liquid contact treatment can be efficiently performed, and the porous body 2 having mesopores is water-permeable.
  • the absorption / desorption layer 4 includes the binder 3 and the water-permeable layer 5 is laminated on the absorption / desorption layer 4, the adhesion / desorption layer 1 is prevented from leaking.
  • Various liquids at the time of the liquid treatment are preferable in that they easily come into contact with the absorption / desorption layer 4.
  • FIG. 1 (c) is an example of a preferred embodiment of the adsorbing / desorbing material 1 having a layer including a porous body 2 having mesopores and a binder 3.
  • the porous body 2 having mesopores adheres to each other with the binder 3.
  • a sheet-like absorption / desorption material 1 is formed.
  • the thickness of the absorbing / desorbing material in a form in which the water-permeable layer is not laminated on the absorbing / desorbing layer is usually 100 ⁇ m or more, preferably 200 ⁇ m or more, and usually 2000 ⁇ m or less, preferably 1000 ⁇ m or less.
  • FIG. 1 (c) is an example of a preferred embodiment of the adsorbing / desorbing material 1 having a layer including a porous body 2 having mesopores and a binder 3.
  • the porous body 2 having mesopores adheres to each other with the binder 3.
  • the shape of the sheet or laminate of the absorbent / desorbent material of the present invention is not particularly limited, and is appropriately determined according to the purpose, such as the form of the biological fluid analyzer to be applied.
  • the sheet means a shape having a width and depth larger than the thickness, but in the present invention, the shape of the sheet or laminate includes a shape having a thickness larger than the width and / or depth.
  • it may be a rectangular parallelepiped whose thickness is longer than the length of one side of the bottom surface, a cylinder whose thickness in the stacking direction is larger than the diameter of the bottom surface, or a cube having the same thickness, width, and depth. It may be.
  • the suction / desorption material 1 of the present invention is inserted into a blood collection spitz (test tube) 10 as shown in FIG. 2A and used in contact with the blood 6 in the spitz 10.
  • a substantially rectangular shape in which one end portion becomes narrower toward the tip end side may be used.
  • the absorbing / desorbing material 1A having a through hole 1a in the thickness direction as shown in FIG. 2B, it is good also as the absorption / desorption material 1B which put the cut 1b in the both sides
  • a configuration may be adopted in which a small piece 1D of the absorbent / desorbing material is placed in the net 7 and suspended by a hanging strap 8 or the like like a tea bag.
  • the adsorbing / desorbing material can be manufactured, for example, by the manufacturing method described below.
  • the adsorbing / desorbing layer is used. 3 by extending the periphery of two water-permeable sheets provided on both sides of the sheet to the outside of the periphery of the absorbing / desorbing layer and heat-sealing the extended portions by heat sealing or the like.
  • the edges of the water-permeable layer 22 and the water-permeable layer 24 are in close contact with each other at the entire peripheral edge portion of the absorbent / desorbable material 26 to form a sealed bag.
  • the width of the heat-sealed portion between the water-permeable layers at the peripheral edge ensures sufficient heat-sealing strength, and absorbs / desorbs the area of the absorbing / desorbing material. From the viewpoint of increasing the layer area ratio and increasing the absorption / desorption efficiency, it is preferably 50 ⁇ m or more, and more preferably 2000 ⁇ m or less.
  • the production method of the adsorbing / desorbing material is not limited.
  • the adsorbing / desorbing material can be produced as follows. First, as shown in FIG. 3A (perspective view), a mask 21 in which a desired pattern is perforated is prepared, and the mask 21 is formed as a water-permeable layer as shown in FIG. 3B (cross-sectional view).
  • a mesoporous silica particle layer 23 is formed in a pattern shape of the through holes 21a of the mask 21 on the water-permeable layer 22 by spreading a porous body having mesopores, for example, mesoporous silica particles, from above. .
  • the water-permeable layer 24 is placed thereon to form a laminate 25 of the water-permeable layer 21 / mesoporous silica particle layer 23 / water-permeable layer 24.
  • a one-dot chain line in FIG. 3D plan view
  • the lower water-permeable layer 22 and the upper water-permeable layer 22 are separated from each other.
  • the water-permeable layer 24 is thermally fused and cut, and as shown in FIG.
  • a sheet-like absorbent / desorbing material having a desired shape including the mesoporous silica particles 23A as the absorbing / desorbing layer. 26 is obtained. Further, by performing pleating, an absorbent / desorbing material 1C shown in FIG. 2 (d) can be obtained.
  • a method of performing heat fusion by heating and then returning to room temperature and then cutting is suitably employed.
  • the porous material having mesopores in the adsorption / desorption layer When the above-mentioned inorganic filler and silica coarse particles are contained together with the porous material having mesopores in the adsorption / desorption layer, the porous material having mesopores and the inorganic filler and / or Alternatively, a mixture of coarse silica particles may be sprayed.
  • the porous body having mesopores and the above-mentioned binder are included in the absorption / desorption layer, the porous body having mesopores and, for example, thermoplastic resin particles as a binder when spraying the porous body having the above-mentioned mesopores.
  • a mixture 25 is sprayed to form a laminate 25 as described above.
  • this laminated body 25 is heated by a hot press, a heating roll, a heating belt or the like, the porous bodies having mesopores and the porous body having mesopores and the water-permeable layer are bonded and integrated by melting the thermoplastic resin. Then cut as above.
  • a mixture of a porous body having mesopores and a binder as needed is sprayed on a water-permeable layer sent out on a belt through a mask, and separately on the mixture. It can implement in the continuous process which piles up the water-permeable layer sent out and heats and cut
  • the absorption / desorption material of the present invention can be used for absorption / desorption of a biological material from a liquid containing the biological material. Therefore, for example, an absorbent / desorbing material can be stored in a container for holding a liquid containing a biological material to obtain a biological material purification kit.
  • the biological material purification kit may include an absorption / desorption material and a container capable of holding the liquid containing the biological material, and the absorption / desorption is performed inside the container for holding the liquid containing the biological material during use. The material may be simply stored (inserted) for use.
  • the material of the container is not limited, it is preferably transparent in order to carry out a biological material absorption / desorption operation, and resin and glass are preferably exemplified.
  • a colored container may be used for the purpose of preventing the biological material from being decomposed by light.
  • the volume of the container is not limited, but is usually 0.1 ml or more, preferably 0.5 ml or more, and the upper limit is not limited, but is usually 1000 L or less, preferably 100 L or less, more preferably 10 L or less. Any volume can be selected according to the purpose.
  • the shape of the container is not limited, it is preferable that the shape of the container and the shape of the adsorbing / desorbing material are shapes that can efficiently perform the liquid contact treatment.
  • examples of the container include a test tube, particularly a microtube.
  • the absorption / desorption material according to the embodiment of the present invention can be applied to a known method of absorbing / desorbing and separating a biological substance from a liquid containing the biological substance.
  • the adsorbing / desorbing material according to the embodiment of the present invention is brought into contact with a liquid containing a biological material, and the biological material is selectively adsorbed in the mesopores of the porous body having mesopores, and then the absorbing / desorbing agent.
  • the biological material can be obtained by washing and desorbing the biological material.
  • the absorption / desorption material when separating a peptide from a biological fluid, specifically blood, the absorption / desorption material is brought into contact with the blood or plasma obtained by processing the blood.
  • the liquid with which the adsorbing / desorbing material is brought into contact preferably has a small content of impurities other than the target biological substance, and known methods can be used for removing the impurities.
  • the adsorption / desorption material is pulled up, as described in Patent Document 1, After washing with water, the porous body is treated with an acidic buffer solution to peel and remove proteins and long-chain peptides adsorbed on the outer surface of the porous body having mesopores, and then treated with a peptide recovery solvent containing acetonitrile.
  • the peptide short chain peptide
  • the peptide separation method using the adsorbent / desorbent according to the embodiment of the present invention is effective for blood tests and peptide analysis, and easily and efficiently automates the analysis of the peptide from the biological fluid with a high recovery rate. Separation and collection enable high-precision analysis. For this reason, it is useful for early detection and diagnosis of cancer, hepatitis, and other diseases. It can also be effectively applied to the recovery and analysis of glycoproteins and glycopeptides.
  • the absorption / desorption material according to the embodiment of the present invention can produce a high-purity peptide, in addition to such test purposes, lifestyle-related disease prevention, blood pressure reduction / stabilization, lipid reduction / stability This is useful for the production of supplements that have effects such as aging and anti-aging.
  • Example 1 The following were used as a porous body having mesopores, a binder, and a water-permeable layer.
  • ⁇ Porous body having mesopores mesoporous silica particles> “Meso Pure” manufactured by Nippon Kasei Co., Ltd.
  • Particle size distribution 70-600 ⁇ m Average particle size: 250 ⁇ m
  • Shape Crushed pore size: 4 nm
  • Pore volume 0.7 ml / g
  • Specific surface area 730 m 2 / g
  • ⁇ Binder Thermoplastic resin particles> EVA (ethylene vinyl acetate copolymer) Water absorption rate: 0.09% Water contact angle: 91 ° MFR: 70g / 10min Melting point: 97 ° C Average particle size: 40 ⁇ m
  • Nonwoven fabric “ZL4035” Constituent fiber: 30% rayon / 70% polyester Fiber average opening: 60 ⁇ m Thickness: 220 ⁇ m Per unit weight: 50 g / m 2 Fiber density: 152.3 kg / m 2 Specific surface area: 0.0003 m 2 / g
  • the mixed powder was obtained by mixing in a mixing container and mixing well so that the weight ratio of mesoporous silica / binder would be 7/3.
  • the obtained mixed powder was uniformly placed on the water-permeable layer so that the basis weight of mesoporous silica was 1000 g / m 2, and the water-permeable layer was further covered thereon to form a sandwich structure.
  • the obtained sandwich structure was thermocompression-bonded at a press pressure of 0.5 MPa, a press temperature of 110 ° C., and a press time of 4 minutes using a desktop test press machine (manufactured by Shinto Metal Industry Co., Ltd.) to produce a molded sheet. .
  • a portion corresponding to 25 mg of mesoporous silica was cut out from the formed molded sheet, and a molded body sample 1 was obtained.
  • LC / MS measuring instrument LC system: Agilent 1200 manufactured by Agilent Technologies Column: Imtakt Presto FT-C18 manufactured by Intact Corporation 4.6 mm ⁇ 30 mm Mass spectrometer: Agilent LC / MS 6130 manufactured by Agilent Technologies, Inc.
  • the molded body sample 1 obtained in Example 1 was placed in an Eppendorf tube having a volume of 1.5 ml, and all the peptide solutions prepared above were further added thereto.
  • the Eppendorf tube was stirred for 1 hour at a rotation speed of 1500 rpm using a vortex mixer (As One Corporation model VM-96B), and the peptide solution was adsorbed to the molded body sample 1. Thereafter, the molded body sample 1 was taken out from the Eppendorf tube and transferred into a 1 ml pipette tip, and then the pipette tip was attached to the quantitative pipette.
  • Example 2 A molded body sample 2 was prepared in the same manner as in Example 1 except that the water-permeable layer shown below was used, and an analytical sample 2 was obtained. This analytical sample 2 was quantified by the peptide quantification method described above. The results are shown in Table 1. ⁇ Water-permeable layer> Non-woven fabric “TM022D” manufactured by Kuraray Co., Ltd. Constituent fiber: Polypropylene fiber thickness: 188 ⁇ m Weight per unit: 23 g / m 2
  • Example 3 A molded body sample 3 was prepared in the same manner as in Example 1 except that the mesoporous silica shown below was used, and an analytical sample 3 was obtained. This analysis sample 3 was quantified by the peptide quantification method described above. The results are shown in Table 1. ⁇ Porous body having mesopores: silica gel> “Carriert G-6” manufactured by Fuji Silysia Chemical Ltd. Particle size distribution: 45 to 150 ⁇ m Shape: Crushed pore size: 6 nm Pore volume: 0.8ml / g Specific surface area: 560 m 2 / g
  • Example 1 From the comparison between Comparative Example 1 and Example 1, the use of the adsorbing / desorbing material of the present invention in the form of a sheet increases the amount of peptide detected rather than using the adsorbing / desorbing material in powder form. It is shown. Moreover, it is clear from the comparison between Example 1 and Example 2 that the amount of peptide recovered is larger when PP (polypropylene) is used as the water-permeable layer. Further, Example 3 using silica gel as a porous material having mesopores has a larger amount of peptide detected than Example 1 using mesoporous silica.
  • the porous body of Example 3 has a smaller particle size than the porous body of Example 1. Since the porous body has a larger surface area that comes into contact with the peptide-containing solution when the particle size is smaller, the volume of the porous body that can contribute to the absorption and desorption of the peptide increases, and it is considered that the recovered amount of peptide is large.
  • Example 4 A model experiment was conducted to examine the effect of the thickness of the water-permeable layer on the amount of peptide recovered.
  • An analysis sample 4 was obtained in the same manner as in Example 1 except that the nonwoven fabric used for the water-permeable layer was cut into a size having the same area as both surfaces of the molded body and tested together with the molded body sample. This analytical sample 4 was quantified by the peptide quantification method described above. The results are shown in Table 2.
  • Example 5 An analysis sample 5 was obtained in the same manner as in Example 1 except that the nonwoven fabric used for the water-permeable layer was cut into a size having the same area as that of one side of the molded body and tested together with the molded body sample. This analytical sample 5 was quantified by the peptide quantification method described above. The results are shown in Table 2.
  • Example 6 A molded body sample 5 was produced in the same manner as in Example 1 except that the mesoporous silica shown below was used, and an analytical sample 6 was obtained. This analytical sample 6 was quantified by the peptide quantification method described above. The results are shown in Table 2.
  • ⁇ Porous body having mesopores mesoporous silica particles> “Meso Pure” manufactured by Nippon Kasei Co., Ltd. used in Example 1 was classified to obtain a porous body having the following particle size distribution and average particle size. Particle size distribution:> 425 ⁇ m Average particle diameter: 566 ⁇ m Shape: Crushed pore size: 4 nm Pore volume: 0.7 ml / g Specific surface area: 730 m 2 / g
  • Example 7 A molded body sample 7 was produced in the same manner as in Example 1 except that the water-permeable layer shown below was used, and an analytical sample 7 was obtained. This analytical sample 7 was quantified by the peptide quantification method described above. The results are shown in Table 2. ⁇ Water-permeable layer> Non-woven fabric “FV-4365” manufactured by Japan Vilene Co., Ltd. Constituent fiber: Polyester fiber
  • Example 8 Except using the water-permeable layer shown below, the molded object sample 8 was produced similarly to Example 1, and the analysis sample 8 was obtained. This analytical sample 8 was quantified by the peptide quantification method described above. The results are shown in Table 2. ⁇ Water-permeable layer> Nonwoven fabric "ELTRS-N" manufactured by Asahi Kasei Corporation Constituent fiber: Nylon fiber
  • Example 9 Except using the water-permeable layer shown below, the molded object sample 9 was produced similarly to Example 1, and the analysis sample 9 was obtained. This analytical sample 9 was quantified by the peptide quantification method described above. The results are shown in Table 2. ⁇ Water-permeable layer> Nonwoven fabric "ELTRS-P" manufactured by Asahi Kasei Corporation Constituent fiber: Polypropylene fiber
  • Example 10 A molded body sample 10 was produced in the same manner as in Example 1 except that the binder shown below was used, and an analytical sample 10 was obtained. This analytical sample 10 was quantified by the peptide quantification method described above. The results are shown in Table 2.
  • the material of the water-permeable layer is preferably PET (polyethylene terephthalate) rather than PP (polypropylene), and PP is more preferred than Nylon (nylon).

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  • Laminated Bodies (AREA)

Abstract

This invention addresses the problem of providing a selective biomaterial adsorption/desorption material for isolating a biomaterial recovery target from a bodily fluid or the like via selective adsorption/desorption; specifically, a selective biomaterial adsorption/desorption material that is easy to handle, makes automation using an analysis device easy, and makes it possible to isolate and recover a biomaterial recovery target quickly, efficiently, and with a high recovery rate. Said problem is solved by a selective biomaterial adsorption/desorption material for isolating a biomaterial recovery target from a biomaterial-containing liquid via selective absorption/desorption, said selective biomaterial adsorption/desorption material being characterized by being a sheet that contains a porous body that has mesopores.

Description

生体物質の選択的吸・脱着材Selective absorption / desorption materials for biological materials
 本発明は、生体物質を含有する液から回収対象とする生体物質を選択的に吸・脱着して分離するための生体物質の選択的吸・脱着材に関し、特に血液等の生体液からペプチド等の生体物質を効率的に分離回収するための生体物質の選択的吸・脱着材に関する。
 本発明はまた、この生体物質の選択的吸・脱着材を用いた高純度ペプチドの製造方法及びペプチドの分離方法に関する。
TECHNICAL FIELD The present invention relates to a biological material selective absorption / desorption material for selectively absorbing / desorbing a biological material to be collected from a biological material-containing liquid, and in particular, a peptide from a biological fluid such as blood. The present invention relates to a biological material selective absorption / desorption material for efficiently separating and recovering biological material.
The present invention also relates to a method for producing a high-purity peptide and a method for separating a peptide using the biological material selective adsorption / desorption material.
 近年、癌や肝炎、その他の疾病の早期発見・診断のためのバイオマーカーとして、血液(血清又は血漿)中のペプチドが注目されている。疾病患者のペプチドには、疾患に特異的なペプチドが存在することから、これを検出することで癌などの疾病の早期発見・診断が可能となる。 In recent years, peptides in blood (serum or plasma) have attracted attention as biomarkers for early detection and diagnosis of cancer, hepatitis, and other diseases. Since peptides specific for diseases exist in peptides of disease patients, early detection / diagnosis of diseases such as cancer becomes possible by detecting these peptides.
 ペプチドをバイオマーカーとして分析するためには、疾病患者から採取した血液からペプチドを選択的に分離回収する必要がある。従来、血液からペプチドを分離回収する方法として、ペプチドがシリカのメソ孔に選択的に侵入して吸着される性質を利用して、メソ孔を有するシリカ(本発明において、「メソポーラスシリカ」と称す。)をペプチドの吸・脱着材として用いる方法が提案されている。 In order to analyze peptides as biomarkers, it is necessary to selectively separate and collect peptides from blood collected from diseased patients. Conventionally, as a method for separating and recovering peptides from blood, silica having mesopores (referred to as “mesoporous silica” in the present invention) by utilizing the property that peptides selectively enter and adsorb into mesopores of silica. .) Has been proposed as a peptide adsorption / desorption material.
 例えば、特許文献1には、血清又は血漿に含まれるペプチドを、ハニカム構造のメソポーラスシリカの乾式粉体と混合することにより、ペプチドをメソポーラスシリカのメソ孔内に吸着させて回収する方法が提案されている。具体的には、まず、メソポーラスシリカの乾式粉体を、ペプチドを含む液体試料に入れて撹拌することにより、ペプチドをメソポーラスシリカのメソ孔内に吸着させた後、遠心分離によりペプチドを吸着したメソポーラスシリカを回収する。回収物を水で洗浄した後、酸性緩衝液で処理することにより、メソポーラスシリカ粒子の外面に吸着している蛋白質ないしは長鎖ペプチドを剥離除去する。次いで水洗後、アセトニトリルを含む水溶液よりなるペプチド回収用溶媒で処理することにより、メソポーラスシリカのメソ孔内に吸着しているペプチド(短鎖ペプチド)を脱着、溶出させて回収し、これを分析する。
 この特許文献1の方法では、メソポーラスシリカの乾式粉体を用いるため、メソポーラスシリカと血液との混合、水による洗浄、酸性緩衝液による処理、ペプチド回収用溶媒による処理の各工程間で、遠心分離によるメソポーラスシリカ粉体の固液分離工程が必要となる。
For example, Patent Document 1 proposes a method in which a peptide contained in serum or plasma is mixed with a dry powder of mesoporous silica having a honeycomb structure so that the peptide is adsorbed and recovered in mesopores of mesoporous silica. ing. Specifically, first, a mesoporous silica powder is adsorbed in a mesopore of mesoporous silica by stirring the dry powder of mesoporous silica in a liquid sample containing the peptide, and then the peptide is adsorbed by centrifugation. Silica is recovered. The recovered product is washed with water and then treated with an acidic buffer to peel and remove proteins or long-chain peptides adsorbed on the outer surface of the mesoporous silica particles. Next, after washing with water, the peptide (short chain peptide) adsorbed in the mesopores of mesoporous silica is recovered by desorption and elution by treating with a peptide recovery solvent consisting of an aqueous solution containing acetonitrile, and this is analyzed. .
In the method of Patent Document 1, since a dry powder of mesoporous silica is used, centrifugation is performed between the steps of mixing mesoporous silica and blood, washing with water, treatment with an acidic buffer, and treatment with a peptide recovery solvent. Requires a solid-liquid separation process of mesoporous silica powder.
国際公開WO2011/062270号パンフレットInternational Publication WO2011 / 062270 Pamphlet
 メソポーラスシリカを用いるペプチドの分離回収方法は、血液中からペプチドを選択的に分離して回収する方法として有効な方法であるが、今後、臨床への実用化に当たっては、分析装置による自動化のために更なる改良が要求される。 The method for separating and recovering peptides using mesoporous silica is an effective method for selectively separating and recovering peptides from blood, but in the future for clinical application, it will be used for automation by analyzers. Further improvements are required.
 即ち、従来法では、メソポーラスシリカを乾式粉体として用い、これをそのまま血液中に投入して撹拌しているため、血液とメソポーラスシリカとの混合工程を含め、水洗、酸性緩衝液による処理、ペプチド回収溶媒による処理の各工程において、粉体と処理液との撹拌混合と遠心分離による固液分離操作を複数回行う必要があり、このように煩雑な操作を複数回必要とする方法を、分析装置を用いて自動化することは困難である。 That is, in the conventional method, mesoporous silica is used as a dry powder, and this is put into blood as it is and stirred. Thus, including the step of mixing blood and mesoporous silica, washing with water, treatment with an acidic buffer, peptide In each step of treatment with the recovered solvent, it is necessary to perform solid-liquid separation operations by stirring and mixing the powder and treatment liquid and centrifuging multiple times, and analyze the method that requires such complicated operations multiple times. It is difficult to automate using an apparatus.
 また、メソポーラスシリカ粉体では、次のような欠点もある。
(1) 液中にメソポーラスシリカの粉体を投入して撹拌しても、十分な接触効率が得られず、ペプチドの吸着効率も脱着効率も低いことから、処理に長時間を要する。
(2) 本来、親水性の高いシリカを粉体の状態で十分に洗浄し、また、遠心分離により固液分離することは困難であり、粉体の懸濁液中に含まれる残留成分のために分析結果が影響を受けるおそれがある。
(3) 遠心分離によるメソポーラスシリカ粉体の回収効率が悪く、ペプチドの回収ロスが多い。ペプチドの回収率が低いことは、分析精度を十分に高めることができない原因ともなる。
(4) 未回収の粉体が閉塞物質ないしは汚染物質となって装置の安定運転を阻害する原因となる。
In addition, mesoporous silica powder has the following drawbacks.
(1) Even if mesoporous silica powder is put into the liquid and stirred, sufficient contact efficiency cannot be obtained, and the peptide adsorption efficiency and desorption efficiency are low, so that the treatment takes a long time.
(2) Originally, it is difficult to thoroughly wash highly hydrophilic silica in a powder state and to separate into solid and liquid by centrifugation, because of residual components contained in the powder suspension. The analysis results may be affected.
(3) The recovery efficiency of mesoporous silica powder by centrifugation is poor, and the recovery loss of peptides is large. The low peptide recovery rate is also a cause of insufficient analysis accuracy.
(4) Unrecovered powder becomes a clogging substance or a pollutant, which hinders stable operation of the device.
 本発明は上記従来の問題点を解決し、生体物質を含有する液から回収対象の生体物質を選択的に吸・脱着して分離するための生体物質の選択的吸・脱着材であって、取り扱い性に優れ、分析装置による自動化が容易であり、回収対象の生体物質を短時間で効率的に、かつ高い回収率で分離回収することができる生体物質の選択的吸・脱着材と、この生体物質の選択的吸・脱着材を用いた高純度ペプチドの製造方法及びペプチドの分離方法を提供することを課題とする。 The present invention solves the above-mentioned conventional problems, is a selective absorption / desorption material of biological material for selectively absorbing / desorbing and separating the biological material to be collected from the liquid containing biological material, This is a material for selective absorption and desorption of biological materials that is easy to handle, easy to be automated by an analyzer, and capable of separating and collecting biological materials to be collected efficiently in a short time and with a high recovery rate. It is an object of the present invention to provide a method for producing a high-purity peptide and a method for separating a peptide using a material for selectively absorbing and desorbing a biological substance.
 本発明者らは、上記課題を解決すべく鋭意検討を重ねた結果、メソ孔を有する多孔体を含むシートを吸・脱着材とすることにより、上記の課題を解決することができることを見出し、本発明を完成させた。 As a result of intensive studies to solve the above problems, the present inventors have found that the above problems can be solved by using a sheet including a porous body having mesopores as an absorbent / desorbing material, The present invention has been completed.
 即ち、本発明は以下を要旨とする。
[1]生体物質を含有する液から、生体物質を選択的に吸・脱着して分離するための生体物質の選択的吸・脱着材であって、該吸・脱着材が、メソ孔を有する多孔体を含むシートであることを特徴とする生体物質の選択的吸・脱着材。
[2]前記吸・脱着材が、メソ孔を有する多孔体を含む吸・脱着層と通水性層とが積層された積層体であることを特徴とする、[1]に記載の生体物質の選択的吸・脱着材。
[3]前記吸・脱着材が、メソ孔を有する多孔体を含む吸・脱着層の両面に通水性層が積層された積層体であることを特徴とする、[2]に記載の生体物質の選択的吸・脱着材。
[4]前記吸・脱着材が、メソ孔を有する多孔体とバインダを含む層を有することを特徴とする、[2]に記載の生体物質の選択的吸・脱着材。
[5]生体物質を含有する液から、生体物質を選択的に吸・脱着して分離するための生体物質の選択的吸・脱着材であって、該吸・脱着材が、メソ孔を有する多孔体を含む吸・脱着層と通水性層とが積層された積層体であることを特徴とする生体物質の選択的吸・脱着材。
[6]生体物質を含有する液から、生体物質を選択的に吸・脱着して分離するための生体物質の選択的吸・脱着材であって、該吸・脱着材が、メソ孔を有する多孔体とバインダとを含む層を有することを特徴とする生体物質の選択的吸・脱着材。
[7]前記メソ孔を有する多孔体のメソ孔径が2nm以上20nm以下である、[1]~[6]のいずれかに記載の生体物質の選択的吸・脱着材。
[8]前記メソ孔を有する多孔体は、平均粒子径が50μm以上700μm以下である、[1]~[7]のいずれかに記載の生体物質の選択的吸・脱着材。
[9]前記メソ孔を有する多孔体は、比表面積が100m/g以上1200m/g以下である、[1]~[8]のいずれかに記載の生体物質の選択的吸・脱着材。
[10]前記メソ孔を有する多孔体は、メソポーラスシリカ、シリカゲル、およびイオン交換樹脂からなる群から選択される1種以上を含む、[1]~[9]のいずれかに記載の生体物質の選択的吸・脱着材。
[11]前記通水性層は、織布又は不織布である、[2]~[5]及び[7]~[10]のいずれかに記載の生体物質の選択的吸・脱着材。
[12]前記通水性層は、外表面に親水化処理が施されている、[2]~[11]のいずれかに記載の生体物質の選択的吸・脱着材。
[13]前記通水性層は、外表面に疎水化処理が施されている、[2]~[12]のいずれかに記載の生体物質の選択的吸・脱着材。
[14]前記生体物質がペプチドである、[1]~[13]のいずれかに記載の生体物質の選択的吸・脱着材。
[15]前記バインダがエチレン酢酸ビニル共重合体である、[4]及び[6]~[14]のいずれかに記載の生体物質の選択的吸・脱着材。
[16]前記バインダは、メソ孔を有する多孔体とバインダとを含む層中に20重量%以上80重量%以下含有される、[4]及び[6]~[15]のいずれかに記載の生体物質の選択的吸・脱着材。
[17]前記生体物質を含有する液を保持しうる容器であって、[1]~[16]のいずれかに記載の吸・脱着材を内部に有する容器。
[18][1]~[16]のいずれかに記載の吸・脱着材と前記生体物質を含有する液を保持しうる容器とを含む生体物質の精製キット。
[19][1]~[16]のいずれかに記載の生体物質の選択的吸・脱着材を、生体物質を含有する液に接触させる工程を含む、生体物質の製造方法。
[20][1]~[16]のいずれかに記載の生体物質の選択的吸・脱着材を、生体物質を含有する液に接触させる工程を含む、生体物質の分離方法。
That is, the gist of the present invention is as follows.
[1] A selective absorption / desorption material for a biological material for selectively absorbing / desorbing a biological material from a liquid containing the biological material, the absorption / desorption material having mesopores A selective absorption / desorption material for a biological material, which is a sheet containing a porous body.
[2] The biological material according to [1], wherein the absorption / desorption material is a laminate in which an absorption / desorption layer including a porous body having mesopores and a water-permeable layer are laminated. Selective absorption / desorption material.
[3] The biological material according to [2], wherein the absorption / desorption material is a laminate in which a water-permeable layer is laminated on both surfaces of an absorption / desorption layer including a porous body having mesopores. Selective suction and desorption material.
[4] The selective adsorption / desorption material for biological material according to [2], wherein the adsorption / desorption material has a porous material having mesopores and a layer containing a binder.
[5] A biological material selective absorption / desorption material for selectively absorbing / desorbing a biological material from a liquid containing the biological material, the absorption / desorption material having mesopores A selective absorption / desorption material for biological materials, characterized in that it is a laminate in which an absorption / desorption layer containing a porous body and a water-permeable layer are laminated.
[6] A selective absorption / desorption material for a biological material for selectively absorbing / desorbing a biological material from a liquid containing the biological material, the absorption / desorption material having mesopores A selective absorption / desorption material for biological materials, comprising a layer containing a porous body and a binder.
[7] The biological material selective adsorption / desorption material according to any one of [1] to [6], wherein the porous body having mesopores has a mesopore diameter of 2 nm to 20 nm.
[8] The selective adsorption / desorption material for biological material according to any one of [1] to [7], wherein the porous body having mesopores has an average particle diameter of 50 μm or more and 700 μm or less.
[9] The selective absorption / desorption material for a biological material according to any one of [1] to [8], wherein the porous body having mesopores has a specific surface area of 100 m 2 / g or more and 1200 m 2 / g or less. .
[10] The biological material according to any one of [1] to [9], wherein the porous body having mesopores includes one or more selected from the group consisting of mesoporous silica, silica gel, and ion exchange resin. Selective absorption / desorption material.
[11] The material for selectively absorbing and desorbing a biological material according to any one of [2] to [5] and [7] to [10], wherein the water-permeable layer is a woven fabric or a nonwoven fabric.
[12] The selective absorption / desorption material for a biological material according to any one of [2] to [11], wherein the water-permeable layer has a hydrophilic treatment on an outer surface.
[13] The selective adsorption / desorption material for a biological material according to any one of [2] to [12], wherein the water-permeable layer has a hydrophobizing treatment on an outer surface.
[14] The selective adsorption / desorption material for biological material according to any one of [1] to [13], wherein the biological material is a peptide.
[15] The selective adsorption / desorption material for a biological material according to any one of [4] and [6] to [14], wherein the binder is an ethylene vinyl acetate copolymer.
[16] The binder according to any one of [4] and [6] to [15], wherein the binder is contained in a layer containing a porous body having mesopores and a binder in an amount of 20 wt% to 80 wt%. Selective absorption / desorption material for biological materials.
[17] A container capable of holding a liquid containing the biological material, the container having the absorption / desorption material according to any one of [1] to [16] inside.
[18] A biological material purification kit comprising the absorption / desorption material according to any one of [1] to [16] and a container capable of holding a liquid containing the biological material.
[19] A method for producing a biological material, comprising the step of bringing the selective adsorption / desorption material for biological material according to any one of [1] to [16] into contact with a liquid containing the biological material.
[20] A method for separating a biological material, comprising the step of bringing the selective absorbing / desorbing material for a biological material according to any one of [1] to [16] into contact with a liquid containing the biological material.
 本発明の生体物質の選択的吸・脱着材によれば、以下のような効果が奏される。 The selective absorption / desorption material for biological materials of the present invention has the following effects.
(1) シート状(層状)の成型体であるため、遠心分離のような固液分離操作が不要であり、例えば、生体物質を含有する液に浸して引き上げるのみで、回収対象の生体物質を吸・脱着層内のメソ孔を有する多孔体に吸着させることができる。また、水洗や各種の処理液による処理についても同様に簡易な操作で行うことができるため、分析装置による自動化が容易である。
(2) 生体物質を含有する液との接触効率が高く、水洗や酸性緩衝液、ペプチド回収溶媒等の処理液による処理の際においてこれらの液体との接触効率も高い。このため、生体物質の吸着効率、脱着効率が高く、生体物質を安定に高収率で分離回収することができる。また、吸着速度、脱着速度、洗浄効率、処理効率が高く、生体物質の吸・脱着操作に要する時間を大幅に短縮することができる。更に、洗浄効率、処理効率が高いことから、好ましくない残留成分の少ない、高純度の生体物質を回収することができ、夾雑物による影響を受けることなく精度よく分析することが可能となる。
(3) メソ孔を有する多孔体が脱落しない設計とすることで、メソ孔を有する多孔体を用いる場合のように、未回収の粉体が閉塞物質ないしは汚染物質となって装置の安定運転を阻害する問題を解決することができる。
(1) Since it is a sheet-like (layered) molded body, solid-liquid separation operation such as centrifugation is unnecessary. For example, the biological material to be collected can be recovered simply by immersing it in a liquid containing biological material and pulling it up. It can be adsorbed to a porous body having mesopores in the adsorption / desorption layer. In addition, since washing with water and treatments with various treatment liquids can be performed with simple operations, automation by an analyzer is easy.
(2) The contact efficiency with a liquid containing a biological substance is high, and the contact efficiency with these liquids is high in the case of treatment with a treatment liquid such as water washing, an acidic buffer solution, and a peptide recovery solvent. Therefore, the adsorption efficiency and desorption efficiency of the biological material are high, and the biological material can be stably separated and recovered with a high yield. Further, the adsorption speed, desorption speed, washing efficiency, and processing efficiency are high, and the time required for the operation of sucking and desorbing the biological material can be greatly shortened. Furthermore, since the washing efficiency and the processing efficiency are high, it is possible to recover a high-purity biological material with few undesirable residual components, and it is possible to perform an accurate analysis without being affected by impurities.
(3) By designing the porous body having mesopores so that it does not fall off, as in the case of using a porous body having mesopores, the unrecovered powder becomes a clogging substance or a pollutant so that the apparatus can be operated stably. The problem of obstruction can be solved.
本発明の生体物質の選択的吸・脱着材の実施の形態を示す、(a)第一の実施形態、(b)第2の実施形態、(c)第3の実施形態の模式的な断面図である。The embodiment of the selective absorption / desorption material for biological materials of the present invention is shown in (a) the first embodiment, (b) the second embodiment, (c) the schematic cross section of the third embodiment. FIG. 本発明の生体物質の選択的吸・脱着材の形状の一例を示す模式図であって、(a)、(d)、(e)図は斜視図、(b)、(c)図は正面図である。It is a schematic diagram which shows an example of the shape of the selective absorption-desorption material of the biological material of this invention, Comprising: (a), (d), (e) figure is a perspective view, (b), (c) figure is a front view FIG. 本発明の生体物質の選択的吸・脱着材の製造方法の一例を示す工程説明図である。It is process explanatory drawing which shows an example of the manufacturing method of the selective absorption / desorption material of the biological material of this invention.
 以下に本発明の実施の形態を詳細に説明する。
 なお、以下において、本発明の実施形態に係る生体物質の選択的吸・脱着材を、生体物質を含有する液と接触させる処理、洗浄のために水と接触させる処理、回収対象の生体物質以外の不要物の剥離除去のために処理液と接触させる処理、回収対象の生体物質の脱着のために生体物質回収用溶媒等の脱着液と接触させる処理等、をまとめて「接液処理」と称する場合がある。
 例えば回収対象の生体物質がペプチド(短鎖ペプチド)の場合、回収対象の生体物質以外の不要物とは、蛋白質ないしは長鎖ペプチド等が挙げられ、不要物の剥離除去のための処理液は酸性緩衝液等が挙げられる。
Hereinafter, embodiments of the present invention will be described in detail.
In the following, the biological material selective absorption / desorption material according to the embodiment of the present invention is brought into contact with a liquid containing the biological material, the treatment is brought into contact with water for cleaning, and the biological material other than the biological material to be collected "Wetted process" is a combination of the process of contacting with a treatment liquid to remove and remove unnecessary materials, the process of contacting with a desorption liquid such as a biological material recovery solvent for desorption of a biological material to be collected, etc. Sometimes called.
For example, when the biological material to be collected is a peptide (short chain peptide), unnecessary substances other than the biological material to be collected include proteins or long-chain peptides, etc., and the treatment liquid for peeling off unnecessary substances is acidic. Examples include a buffer solution.
[生体物質の選択的吸・脱着材]
 本実施形態に係る生体物質の選択的吸・脱着材は、メソ孔を有する多孔体を含むシートである形態(以下、第1の実施形態ともいう。)を含む。
 また、本実施形態に係る吸・脱着材の別の実施形態として、メソ孔を有する多孔体を含む吸・脱着材と通水性層とが積層された積層体であってもよい(以下、第2の実施形態ともいう。)。
 また、本実施形態に係る吸・脱着材の別の実施形態として、メソ孔を有する多孔体とバインダとを含む層を有してもよい(以下、第3の実施形態ともいう)。
[Selective absorption and desorption material for biological materials]
The biological material selective absorption / desorption material according to the present embodiment includes a form (hereinafter, also referred to as a first embodiment) which is a sheet including a porous body having mesopores.
Further, another embodiment of the adsorbing / desorbing material according to the present embodiment may be a laminate in which an adsorbing / desorbing material including a porous body having mesopores and a water-permeable layer are laminated (hereinafter referred to as the first). 2).
In addition, as another embodiment of the adsorbing / desorbing material according to the present embodiment, a layer including a porous body having mesopores and a binder may be included (hereinafter also referred to as a third embodiment).
 本発明の吸・脱着材は、メソ孔を有する多孔体を含み、シート状構造を有するものであれば特に制限はないが、例えば血液の凝固因子となるような血栓性材料は好ましくなく、選択的吸・脱着材全体として、生体不活性材料や抗血栓性材料などの生体適合性材料よりなることが好ましい。
 ただし、生体不適合性材料であっても、表面処理等により生体液との接触面が血栓性材料や生体不活性材料よりなるものとされたものは、生体適合性材料として、生体物質の選択的吸・脱着材の構成材料として用いることができる。
The absorption / desorption material of the present invention is not particularly limited as long as it includes a porous body having mesopores and has a sheet-like structure. However, for example, a thrombotic material that becomes a blood coagulation factor is not preferable. The overall adsorbent / desorbable material is preferably made of a biocompatible material such as a bioinert material or an antithrombotic material.
However, even in the case of bioincompatible materials, those in which the contact surface with the biological fluid is made of a thrombotic material or a bioinert material by a surface treatment or the like is selected as a biocompatible material. It can be used as a constituent material of the absorption / desorption material.
 また、第1の実施形態に係る吸・脱着材は、以下のような特性ないし条件を有することが望まれることから、そのための様々な処理やシート設計上の工夫を講じることが好ましい。
(1)メソ孔を有する多孔体が生体物質を選択的に吸・脱着することから、生体物質の回収量を増加させるためには、吸・脱着材に含まれるメソ孔を有する多孔体の内表面積およびメソ孔の表面積と細孔容積がともに大きいことが好ましい。
(2) 接液処理時の液との接触効率を上げるために吸・脱着材に含まれる多孔体の外表面積を大きくすることが好ましい。多孔体の外表面積を大きくするためには、例えば、多孔体の粒径を小さくしたり、吸・脱着層を薄くすればよい。
(3) 接液処理時の液との接触効率を上げるために、メソ孔を有する多孔体は接液処理時の液との濡れ性がよいことが好ましい。また、吸・脱着材を構成する各部材、例えば通水性層を構成する材料に親水化処理を施したり、液中に浸漬し易いように吸・脱着材の比重を調整することが好ましい。
(4)吸・脱着材に含まれるメソ孔を有する多孔体は、接液処理時に流動しても流動しなくてもよい。液との接触効率の面からは流動した方が好ましい。流動が激し過ぎると、メソ孔を有する多孔体同士の衝突で粒子が破損し、細かい多孔体粉体が発生して脱落する「粉もれ」が起きる可能性がある。従って、脱落した多孔体粉体が、装置の閉塞因子又は汚染因子となると共に、ペプチドの回収率も悪くなるため、流動の程度は粉もれがない程度に調整することが好ましい。一方、粉もれを抑止し、取り扱い性を向上するためには接液処理時に多孔体が流動しない方が好ましい。流動しないためには多孔体をバインダで固定することが好ましい。
In addition, since the adsorbing / desorbing material according to the first embodiment is desired to have the following characteristics or conditions, it is preferable to devise various processing and sheet design for that purpose.
(1) Since the porous material having mesopores selectively absorbs and desorbs biological materials, in order to increase the amount of collected biological materials, the porous materials having mesopores contained in the absorption / desorption material It is preferable that both the surface area and the surface area of the mesopores and the pore volume are large.
(2) It is preferable to increase the outer surface area of the porous body contained in the adsorption / desorption material in order to increase the efficiency of contact with the liquid during the liquid contact treatment. In order to increase the outer surface area of the porous body, for example, the particle diameter of the porous body may be reduced, or the absorption / desorption layer may be thinned.
(3) In order to increase the contact efficiency with the liquid during the liquid contact treatment, the porous body having mesopores preferably has good wettability with the liquid during the liquid contact treatment. Moreover, it is preferable that each member constituting the absorbent / desorbing material, for example, a material constituting the water-permeable layer is subjected to a hydrophilic treatment, or the specific gravity of the absorbent / desorbing material is adjusted so as to be easily immersed in the liquid.
(4) The porous body having mesopores contained in the absorption / desorption material may or may not flow during the liquid contact treatment. From the viewpoint of contact efficiency with the liquid, it is preferable that the fluid flows. If the flow is too intense, the particles may be damaged by the collision between the porous bodies having mesopores, and there is a possibility that "powdery" occurs where fine porous powder is generated and dropped. Therefore, the dropped porous powder becomes a clogging factor or a contamination factor of the apparatus, and the recovery rate of the peptide also deteriorates. Therefore, it is preferable to adjust the degree of flow to such an extent that no powder leaks. On the other hand, it is preferable that the porous body does not flow during the liquid contact treatment in order to suppress powder leakage and improve the handleability. In order not to flow, the porous body is preferably fixed with a binder.
 なお、第2の実施形態及び第3の実施形態に係る吸・脱着材に関しても、対応する上記説明が援用され得る。また、以下に示す発明の構成要件に関する説明も、第1の実施形態のみならず、第2の実施形態及び第3の実施形態に係る吸・脱着材に関して援用され得る。「本発明の実施形態」との表記は、第1の実施形態、第2の実施形態及び第3の実施形態を含み、またそれ以外の本発明が含み得る実施形態を全て包含する。 In addition, the said description corresponding to the suction / desorption material which concerns on 2nd Embodiment and 3rd Embodiment can be used. Moreover, the description regarding the component requirements of the invention shown below can be applied not only to the first embodiment but also to the absorption / desorption materials according to the second embodiment and the third embodiment. The expression “embodiment of the present invention” includes the first embodiment, the second embodiment, and the third embodiment, and includes all other embodiments that the present invention can include.
<生体物質を含有する液・生体物質>
 本発明の実施形態において処理対象となる生体物質を含有する液としては、代表的には生体液である血液(血清又は血漿)が挙げられるが、これに限らず、例えば生体内に存在する体液、或いは生体内から外部へ排出される液、およびこれらの処理液のすべてが包含される。処理液とは生体液に処理を施した液であり、生体物質を分離回収できればその処理方法は限定されず、公知の方法を適用することができる。また、生体は人体に限定されない。生体液としては、具体的には以下のものが例示されるが、何らこれらに限定されるものではない。
 血液、リンパ液、組織液(組織間液、細胞間液、間質液)、胸水、腹水、心嚢液等の漿膜腔液、脳脊髄液(髄液)、関節液(滑液)、眼房水(房水)、唾液、胃液、胆汁、膵液、腸液等の消化液、汗、涙、鼻水、尿、精液、膣液、羊水、乳汁。
<Liquids and biological substances containing biological substances>
In the embodiment of the present invention, the liquid containing the biological material to be processed typically includes blood (serum or plasma) which is a biological fluid, but is not limited thereto, for example, a biological fluid present in the living body. Alternatively, the liquid discharged from the living body to the outside and all of these processing liquids are included. The treatment liquid is a liquid obtained by treating a biological fluid, and the treatment method is not limited as long as the biological substance can be separated and recovered, and a known method can be applied. Further, the living body is not limited to the human body. Specific examples of biological fluids include, but are not limited to, the following.
Blood, lymph, tissue fluid (interstitial fluid, intercellular fluid, interstitial fluid), pleural effusion, ascites, serous fluid such as pericardial fluid, cerebrospinal fluid (spinal fluid), joint fluid (synovial fluid), aqueous humor ( Aqueous humor), saliva, gastric juice, bile, pancreatic juice, intestinal juice, etc., sweat, tears, runny nose, urine, semen, vaginal fluid, amniotic fluid, milk.
 生体物質を含有する液から分離回収する生体物質としては、メソ孔を有する多孔体内に選択的に侵入して吸着されるものであればよく特に制限はないが、疾病の早期発見・診断のためのバイオマーカーとして使用できる生体物質が好ましく、例えば、核酸由来のバイオマーカー、ペプチド、タンパク質、脂質代謝物、糖質代謝物等が挙げられる。核酸としてはDNAおよびRNAがあげられる。
 生体物質の液中での動的直径は、通常0.3nm以上、好ましくは0.4nm以上、より好ましくは0.5nm以上であり、通常15nm以下、好ましくは12nm以下、よりお好ましくは10nm以下である。生体物質がペプチドの場合、特にアミノ酸残基長10~100、好ましくは10~50の短鎖ペプチドが挙げられる。
 生体物質を含有する液は分離回収の対象となる生体物質以外の不純物の含有量は少ない方が好ましく、不純物は公知の方法で除去できる。例えば、生体物質がペプチドの場合、アルブミンやグロブリンなどのタンパク質等の不純物の含有量が少ない方が好ましい。
The biological material to be separated and recovered from the liquid containing the biological material is not particularly limited as long as it is selectively penetrated and adsorbed into the porous body having mesopores, but for early detection and diagnosis of diseases. Biological substances that can be used as biomarkers are preferably, for example, biomarkers derived from nucleic acids, peptides, proteins, lipid metabolites, carbohydrate metabolites, and the like. Examples of the nucleic acid include DNA and RNA.
The dynamic diameter of the biological material in the liquid is usually 0.3 nm or more, preferably 0.4 nm or more, more preferably 0.5 nm or more, and usually 15 nm or less, preferably 12 nm or less, more preferably 10 nm or less. It is. When the biological substance is a peptide, a short chain peptide having an amino acid residue length of 10 to 100, preferably 10 to 50 is particularly mentioned.
The liquid containing the biological material preferably has a small content of impurities other than the biological material to be separated and recovered, and the impurities can be removed by a known method. For example, when the biological substance is a peptide, it is preferable that the content of impurities such as proteins such as albumin and globulin is small.
<メソ孔を有する多孔体>
 メソ孔を有する多孔体としては、メソ孔を有しており、且つ多孔体であれば特段限定されない。具体的には、メソポーラスシリカ、シリカゲル、シリカ・アルミナ、イオン交換樹脂、珪藻土、活性炭、ゼオライト、酸性白土、などがあげられる。これらのうち、生体物質の吸脱着の観点から、メソポーラスシリカ、シリカゲル、イオン交換樹脂であることが好ましい。
 メソ孔の細孔径は通常2nm以上であり、また通常50nm以下、好ましくは20nm以下、より好ましくは10nm以下、更に好ましくは8nm以下、特に好ましくは5nm以下である。
 メソ孔の細孔径は、分離回収の目的物である生体物質の種類に応じて設定することが好ましい。例えばペプチドを分離回収するためには、通常1nm以上、好ましくは2nm以上、より好ましくは3nm以上であり、通常15nm以下、好ましくは12nm以下、よりこのましくは10nm以下である。
<Porous body having mesopores>
The porous body having mesopores is not particularly limited as long as it has mesopores and is a porous body. Specific examples include mesoporous silica, silica gel, silica / alumina, ion exchange resin, diatomaceous earth, activated carbon, zeolite, and acid clay. Of these, mesoporous silica, silica gel, and ion exchange resin are preferable from the viewpoint of adsorption and desorption of biological substances.
The mesopore diameter is usually 2 nm or more, and usually 50 nm or less, preferably 20 nm or less, more preferably 10 nm or less, still more preferably 8 nm or less, and particularly preferably 5 nm or less.
The pore diameter of the mesopores is preferably set according to the type of biological material that is the target of separation and recovery. For example, in order to separate and recover peptides, it is usually 1 nm or more, preferably 2 nm or more, more preferably 3 nm or more, usually 15 nm or less, preferably 12 nm or less, more preferably 10 nm or less.
 メソ孔を有する多孔体は、メソ孔を有していれば、メソ孔に含まれないマクロ孔などの細孔を有していてもよいが、目的とする生体物質を選択性よく効率的に分離回収するために、メソ孔を有する多孔体の細孔はメソ孔のみからなるものが好ましい。
 なお、メソ孔を有する多孔体の細孔径は、窒素ガス吸脱着法で測定した等温吸・脱着曲線から、E.P.Barrett, L.G.Joyner, P.H.Haklenda, J.Amer.Chem.Soc.,vol.73,373(1951)に記載のBJH法により算出される細孔分布曲線、即ち、細孔直径d(nm)に対して微分窒素ガス吸着量(ΔV/Δ(logd);Vは窒素ガス吸着容積)をプロットした図から求めることができるが、市販品についてはカタログ値を採用することができる。
A porous body having mesopores may have pores such as macropores that are not included in the mesopores as long as it has mesopores. In order to separate and recover, the porous body having mesopores preferably has only mesopores.
The pore diameter of the porous body having mesopores was determined from EP Barrett, LG Joyner, PHHaklenda, J. Amer. Chem. Soc., Vol. 73, 373 (1951 Plot distribution curve calculated by the BJH method described in the above), that is, the differential nitrogen gas adsorption amount (ΔV / Δ (logd); V is the nitrogen gas adsorption volume) is plotted against the pore diameter d (nm). Although it can be obtained from the figure, catalog values can be adopted for commercial products.
 また、メソ孔を有する多孔体の単位重量当たりの細孔容積(本明細書ではこの「細孔容積/重量」で表される量を、単に「細孔容積」という。)は、通常0.1ml/g以上、好ましくは0.2ml/g以上、また通常1.5ml/g以下、好ましくは1.2ml/g以下である。細孔容積が上記下限未満では、吸・脱着性能に劣る傾向があり、上記上限を超えると接液処理で細孔構造や粒子が壊れやすくなり吸・脱着選択性が低下したり、粉もれが発生したりする。メソ孔を有する多孔体の細孔容積は、吸着等温線の相対圧0.98における窒素ガスの吸着量から求めることができるが、市販品についてはカタログ値を採用することができる。 Further, the pore volume per unit weight of the porous body having mesopores (in this specification, the amount represented by “pore volume / weight” is simply referred to as “pore volume”) is usually 0.00. 1 ml / g or more, preferably 0.2 ml / g or more, and usually 1.5 ml / g or less, preferably 1.2 ml / g or less. If the pore volume is less than the above lower limit, the adsorption / desorption performance tends to be inferior, and if the upper limit is exceeded, the pore structure and particles are easily broken by the liquid contact treatment, and the adsorption / desorption selectivity is reduced, or the powder leaks. May occur. The pore volume of the porous body having mesopores can be determined from the amount of nitrogen gas adsorbed at a relative pressure of 0.98 of the adsorption isotherm, but a catalog value can be adopted for a commercial product.
 メソ孔を有する多孔体の形状は、多孔体をシート状(層状)に成型可能であれば特に制限はなく、破砕状、球状等の粒状であってもよく、また、モノリスや造粒粒子であってもよい。また、特許文献1に記載されるハニカム構造のものであってもよい。造粒粒子の場合は、一次粒子間の空隙が大きいものが、生体液等との接触効率の面で好ましい。 The shape of the porous body having mesopores is not particularly limited as long as the porous body can be formed into a sheet (layered) shape, and may be in the form of a crushed shape, a spherical shape, or a monolith or granulated particle. There may be. Moreover, the thing of the honeycomb structure described in patent document 1 may be sufficient. In the case of granulated particles, those having large gaps between primary particles are preferable in terms of contact efficiency with biological fluids and the like.
 メソ孔を有する多孔体の大きさは、小さ過ぎると、全表面積(メソ孔内表面積と粒子外表面積との合計)に対して粒子外表面積が大きくなり、吸着効率、液との接触効率の面では有利である反面、吸着物質によっては、吸着選択性が下がるおそれがあり、逆に、大きい粒子では、粒子内の細孔長が長いために、接液処理時に生体液や洗浄水又は処理液が細孔内に浸透、拡散するのに時間がかかるようになり、吸・脱着や洗浄、生体物質の回収に長時間を要し、好ましくない。 If the size of the porous body having mesopores is too small, the surface area outside the particle will increase with respect to the total surface area (the total surface area inside the mesopore and the surface area outside the particle). On the other hand, depending on the adsorbing substance, there is a risk that the adsorption selectivity may be lowered. Conversely, for large particles, the pore length in the particles is long. It takes time to penetrate and diffuse into the pores, and it takes a long time for absorption / desorption, washing, and collection of biological materials, which is not preferable.
 メソ孔を有する多孔体の大きさには、回収対象の生体物質等に応じて最適値があり、一概には規定できないが、例えば、全粒子の80%以上、好ましくは90%以上、より好ましくは95%以上の粒子の最大フェレ径が、好ましくは20μm以上であり、より好ましくは50μm以上であり、好ましくは1mm以下であり、より好ましくは800μm以下である。
 平均粒子径は、好ましくは50μm上、より好ましくは70μm以上であり、好ましくは700μm以下であり、より好ましくは600μm以下である。
The size of the porous body having mesopores has an optimum value according to the biological material to be collected and cannot be defined unconditionally. For example, it is 80% or more, preferably 90% or more, more preferably, of all particles. The maximum ferret diameter of 95% or more of the particles is preferably 20 μm or more, more preferably 50 μm or more, preferably 1 mm or less, more preferably 800 μm or less.
The average particle diameter is preferably 50 μm or more, more preferably 70 μm or more, preferably 700 μm or less, more preferably 600 μm or less.
 ここで、最大フェレ径とはいわゆる定方向接線径の最大値であり、球状粒子であればその直径に該当し、破砕状等の異形形状の粒子では、その粒子を2本の平行な定方向接線で挟んだ場合に、最もその線同士の間の間隔が長くなる箇所の長さに該当する。最大フェレ径は例えば、光学顕微鏡により粒子を観察し、画像解析を行うことで求めることができる(以下、最大フェレ径を「粒子サイズ」ということがある)。全粒子に占める所定の径の粒子の割合は、任意に100個以上の粒子を選択して求めることができる。
 また、平均粒子径は一次粒子の粒子サイズの平均値である。平均粒子径は、レーザー回折・散乱式粒度分布測定装置(例えば、セイシン企業製レーザーマイクロンサイザーLMS-24)等によって粒度分布を測定し、その結果から求めることができるが、市販品についてはカタログ値を採用することができる。
Here, the maximum ferret diameter is the maximum value of the so-called directional tangent diameter, which corresponds to the diameter of spherical particles, and in the case of irregularly shaped particles such as crushed particles, the particles are divided into two parallel fixed directions. When sandwiched between tangent lines, this corresponds to the length of the part where the distance between the lines is the longest. The maximum ferret diameter can be determined, for example, by observing particles with an optical microscope and performing image analysis (hereinafter, the maximum ferret diameter may be referred to as “particle size”). The ratio of particles having a predetermined diameter in all particles can be determined by arbitrarily selecting 100 or more particles.
The average particle diameter is an average value of the particle sizes of the primary particles. The average particle size can be obtained from the particle size distribution measured by a laser diffraction / scattering type particle size distribution analyzer (for example, Laser Micron Sizer LMS-24 manufactured by Seishin Enterprise). Can be adopted.
 メソ孔を有する多孔体は、比表面積が通常100m/g以上であり、好ましくは200m/gであり、また通常1200m/g以下、好ましくは1000m/g以下である。比表面積が上記下限以上であることで、目的物を効率的に吸・脱着することができる。上記上限以下であることで、多孔体の強度を担保することができ、吸・脱着材の耐久性を向上することができる。
 なお、比表面積は、BET1点法により測定される。
The porous body having mesopores has a specific surface area of usually 100 m 2 / g or more, preferably 200 m 2 / g, and usually 1200 m 2 / g or less, preferably 1000 m 2 / g or less. When the specific surface area is at least the above lower limit, the target product can be efficiently absorbed and desorbed. By being below the above upper limit, the strength of the porous body can be ensured and the durability of the absorbent / desorbable material can be improved.
The specific surface area is measured by the BET single point method.
 メソ孔を有する多孔体は、外表面に目的物質以外の物質が吸着するのを防ぐために、疎水化処理等の表面処理を施して用いてもよい。表面処理の例としては、メソ孔を有する多孔体の外表面をシリコーン処理、トリメチルシリル化処理することで疎水化して、メソ孔を有する多孔体の細孔内のみに目的とする生体物質が選択的に吸着するように改質してもよい。この場合、メソ孔を有する多孔体の細孔内にもこのような処理が施されると、細孔内で目的物質が吸着し難くなるため、粒子の外表面のみに表面処理が施されるように、その処理の程度を調整することが重要である。 The porous body having mesopores may be used after being subjected to a surface treatment such as a hydrophobization treatment in order to prevent substances other than the target substance from adsorbing to the outer surface. As an example of surface treatment, the outer surface of a porous body having mesopores is hydrophobized by silicone treatment and trimethylsilylation treatment, and the target biological material is selectively contained only in the pores of the porous body having mesopores. You may modify | reform so that it may adsorb | suck to. In this case, if such a treatment is also performed in the pores of the porous body having mesopores, it becomes difficult for the target substance to be adsorbed in the pores, so that the surface treatment is performed only on the outer surface of the particles. Thus, it is important to adjust the degree of the processing.
 <吸・脱着層>
 吸・脱着層はメソ孔を有する多孔体のみで構成されていてもよく、メソ孔を有する多孔体と他の材料とで構成されていてもよい。
 吸・脱着層に含まれていてもよいメソ孔を有する多孔体以外の材料としては、メソ孔を有する多孔体による生体物質の吸・脱着機能を大きく阻害することなく、また生体不活性材料よりなるものであれば特に制限はないが、例えば、メソ孔を有する多孔体を固定して吸・脱着層の成型安定性を高め、前述の粉もれを防止するためのバインダや、比重調整のための無機フィラー、濡れ性向上のためのシリカの粗大粒子などが挙げられる。
 本発明の第1の実施態様は、接液処理時に吸・脱着層を構成する材料が流動する態様を含むが、その場合、吸・脱着層にバインダを含んでも含まなくてもよい。
<Suction / desorption layer>
The absorption / desorption layer may be composed only of a porous body having mesopores, or may be composed of a porous body having mesopores and another material.
As materials other than porous bodies having mesopores that may be contained in the absorption / desorption layer, the material having the mesopores does not significantly impair the absorption / desorption function of biological substances, and more There is no particular limitation as long as it is, but, for example, fixing a porous body having mesopores to improve the molding stability of the absorption / desorption layer, a binder for preventing the above-mentioned powder leakage, and adjusting the specific gravity Inorganic filler for the purpose, coarse particles of silica for improving the wettability.
The first embodiment of the present invention includes an aspect in which the material constituting the absorption / desorption layer flows during the liquid contact treatment. In this case, the absorption / desorption layer may or may not include a binder.
<バインダ>
 バインダは、メソ孔を有する多孔体を成型できれば特に限定されないが、熱可塑性樹脂が好ましく用いられる。熱可塑性樹脂としては、メソ孔を有する多孔体を成型(例えば熱融着により接着)することができるものであればよく特に制限はない。好ましくは以下に記載する吸水率及びMFRを満足するものであり、例えば、ポリエチレン、ポリプロピレン、エチレン酢酸ビニル共重合体、ポリ酢酸ビニル、ケン化エチレン酢酸ビニル共重合体、ポリビニルアルコール、ポリエステル、ポリアミド、ポリウレタン、アイオノマー樹脂などがあげられ、これらの変性物であってもよい。多孔体の成型性及び溶剤耐性の観点から、エチレン酢酸ビニル共重合体、ケン化エチレン酢酸ビニル共重合体、ポリエステル、ポリアミド、ポリエチレンが好ましい。中でも、成分の溶出が少なく、メソ孔を有する多孔体の吸・脱着特性を低下させづらく、吸・脱着材に外部応力を受けてもメソ孔を有する多孔体が脱落しづらい点で、エチレン酢酸ビニル共重合体がより好ましい。
<Binder>
The binder is not particularly limited as long as a porous body having mesopores can be molded, but a thermoplastic resin is preferably used. The thermoplastic resin is not particularly limited as long as it can mold a porous body having mesopores (for example, adhesion by thermal fusion). Preferably, the water absorption and MFR described below are satisfied. For example, polyethylene, polypropylene, ethylene vinyl acetate copolymer, polyvinyl acetate, saponified ethylene vinyl acetate copolymer, polyvinyl alcohol, polyester, polyamide, Examples thereof include polyurethane, ionomer resin, and the like. From the viewpoint of moldability and solvent resistance of the porous body, ethylene vinyl acetate copolymer, saponified ethylene vinyl acetate copolymer, polyester, polyamide, and polyethylene are preferable. Among them, ethylene acetic acid has the advantage that the elution of the components is small, the absorption / desorption characteristics of the porous body having mesopores are difficult to deteriorate, and the porous body having mesopores is not easily dropped even if the absorption / desorption material is subjected to external stress. A vinyl copolymer is more preferable.
 熱可塑性樹脂は、以下の方法で測定される吸水率が0.2%以上であることが好ましい。吸水率が0.2%未満の熱可塑性樹脂は、疎水性が強く、吸・脱着層において、メソポーラスシリカ粒子間の空隙に表出した熱可塑性樹脂が水をはじくことによって、吸・脱着材の吸・脱着性能が劣るものとなる場合がある。熱可塑性樹脂の吸水率は高い程好ましく、特に0.5%以上であることが好ましい。熱可塑性樹脂の吸水率の上限としては、通常10%以下である。 It is preferable that the thermoplastic resin has a water absorption rate of 0.2% or more measured by the following method. A thermoplastic resin having a water absorption rate of less than 0.2% is highly hydrophobic, and in the absorption / desorption layer, the thermoplastic resin exposed in the gaps between the mesoporous silica particles repels water, so that the absorption / desorption material Absorption / desorption performance may be inferior. The higher the water absorption rate of the thermoplastic resin, the more preferable, and particularly 0.5% or more is preferable. The upper limit of the water absorption rate of the thermoplastic resin is usually 10% or less.
(熱可塑性樹脂の吸水率)
 ポリエステル製剥離フィルム又はアルミ箔上に熱可塑性樹脂粒子を均一に散布した後、この上にポリエステル製剥離フィルム又はアルミ箔を重ね合わせて熱可塑性樹脂粒子を挟持させ、次いでこの積層体をホットプレスにより、熱可塑性樹脂粒子の融点よりも10℃高い温度にて0.5MPaで2分間処理し、その後、剥離フィルム又はアルミ箔を剥がし取り、吸水率測定用フィルム(厚さ約1mm)を作成する。このフィルムを25℃の水に3時間浸漬した後引き上げ、吸水性の良い紙にはさみ込んで表面の水滴を取り去った後、重量を測定し、重量増加分から吸水率(=重量増加分/吸水前の重量×100)を算出する。
(Water absorption rate of thermoplastic resin)
After the thermoplastic resin particles are uniformly dispersed on the polyester release film or aluminum foil, the polyester release film or aluminum foil is laminated on the polyester release film or aluminum foil to sandwich the thermoplastic resin particles, and then this laminate is hot-pressed. Then, the film is treated at 0.5 MPa for 2 minutes at a temperature 10 ° C. higher than the melting point of the thermoplastic resin particles, and then the release film or the aluminum foil is peeled off to prepare a film for measuring water absorption (thickness: about 1 mm). This film is immersed in water at 25 ° C. for 3 hours and then pulled up. The film is sandwiched in paper with good water absorption to remove water droplets on the surface, and the weight is measured. From the weight increase, the water absorption rate (= weight increase / before water absorption) Weight × 100).
 熱可塑性樹脂の吸水率は、熱可塑性樹脂の親水性の指標として用いているが、熱可塑性樹脂の親水性は、水接触角によっても表すことができる。熱可塑性樹脂は、これを前述の吸水率測定用フィルムと同様の方法でフィルム状とし、このフィルム面に対してθ/2法により測定した水接触角が95°以下、特に85°以下であることが好ましい。前述の吸水率とこの水接触角とは必ずしも対応しておらず、水接触角が小さくても吸水率が低い熱可塑性樹脂や、吸水率が大きくても水接触角が大きい熱可塑性樹脂もある。これら両方の特性の指標とした場合、吸水率が大きくかつ水接触角が小さいものが最も好ましいが、吸水率が0.2%程度で、比較的吸水率の低いものであっても水接触角が小さいものであれば本発明に有効であると言える。 The water absorption rate of the thermoplastic resin is used as an index of hydrophilicity of the thermoplastic resin, but the hydrophilicity of the thermoplastic resin can also be expressed by a water contact angle. The thermoplastic resin is formed into a film by the same method as the film for measuring water absorption described above, and the water contact angle measured by the θ / 2 method with respect to the film surface is 95 ° or less, particularly 85 ° or less. It is preferable. The water absorption rate described above does not necessarily correspond to this water contact angle, and there are thermoplastic resins having a low water absorption rate even if the water contact angle is small, and thermoplastic resins having a large water contact angle even if the water absorption rate is large. . When both of these characteristics are used as an index, the water absorption rate is large and the water contact angle is small, but the water contact angle is about 0.2%, even if the water absorption rate is relatively low. If it is small, it can be said that it is effective for the present invention.
 熱可塑性樹脂はまた、以下の方法で測定されるMFRが55g/10min以下であることが好ましい。MFRが55g/10minを超えるような流動性の大きいものでは、熱融着時の流動で、メソ孔を有する多孔体の表面を広く覆うこととなり、メソ孔を有する多孔体の表出面積を低減させ、また、メソ孔を有する多孔体の細孔をふさいでしまい、メソ孔を有する多孔体本来の吸・脱着機能を有効に発揮し得なくなる場合がある。熱可塑性樹脂のMFRは小さいほうが好ましいが、MFRが過度に小さいものは熱溶融時の流動性が小さ過ぎて、メソ孔を有する多孔体の成型が困難になる場合がある。従って、熱可塑性樹脂のMFRは1~55g/10min、特に5~50g/10minであることが好ましい。 The thermoplastic resin also preferably has an MFR measured by the following method of 55 g / 10 min or less. When the fluidity is high such that the MFR exceeds 55 g / 10 min, the surface of the porous body having mesopores is widely covered by the flow at the time of heat fusion, and the exposed area of the porous body having mesopores is reduced. In addition, the pores of the porous body having mesopores may be blocked, and the inherent absorption / desorption function of the porous body having mesopores may not be effectively exhibited. The thermoplastic resin preferably has a small MFR, but if the MFR is too small, the fluidity at the time of heat melting is too small, and it may be difficult to mold a porous body having mesopores. Therefore, the MFR of the thermoplastic resin is preferably 1 to 55 g / 10 min, particularly 5 to 50 g / 10 min.
(熱可塑性樹脂のMFR)
 JIS K6760に従って、190℃、2.16kg荷重で測定する。
(MFR of thermoplastic resin)
Measured according to JIS K6760 at 190 ° C. and 2.16 kg load.
 熱可塑性樹脂の融点について特に制限はないが、通常50℃以上、好ましくは80℃以上、また通常250℃以下、好ましくは150℃以下である。熱可塑性樹脂の融点が50℃未満の場合は、常温での使用において熱変形しやすいという問題があり、逆に、250℃を超えると吸・脱着層の加熱溶融成形時に、後述の通水性層を備える場合には、該通水性層を熱変形させてしまうおそれがある。 Although there is no restriction | limiting in particular about melting | fusing point of a thermoplastic resin, Usually, 50 degreeC or more, Preferably it is 80 degreeC or more, and is usually 250 degrees C or less, Preferably it is 150 degrees C or less. When the melting point of the thermoplastic resin is less than 50 ° C., there is a problem that the thermoplastic resin is likely to be thermally deformed when used at room temperature. In the case where the water-permeable layer is provided, the water-permeable layer may be thermally deformed.
 熱可塑性樹脂の形状は特に限定されないが、粒子状のものを用いることで、メソ孔を有する多孔体と熱可塑性樹脂とを混合し、プレスする方法で、吸着脱層であるシートを形成することができる。熱可塑性樹脂粒子を用いる場合には、メソ孔を有する多孔体の粒子径との関係において、好適な粒子径が存在する。メソ孔を有する多孔体の粒子径に対して、熱可塑性樹脂粒子の粒子径が過度に大きいと、メソ孔を有する多孔体間に良好な空隙を形成し得ず、また、シート形成時に熱可塑性樹脂粒子中にメソ孔を有する多孔体が埋没してしまい、十分な吸・脱着機能を発揮することができない場合がある。熱可塑性樹脂粒子の粒子径が過度に小さくても、メソ孔を有する多孔体同士が密接し、吸・脱着層の空隙率が小さくなってしまう。粒子径が過度に小さい熱可塑性樹脂粒子は市販品として入手し難く、またメソ孔を有する多孔体との均一混合性にも劣るという欠点がある。 The shape of the thermoplastic resin is not particularly limited, but by using a particulate material, a porous body having mesopores and the thermoplastic resin are mixed and pressed to form a sheet that is an adsorption delayer. Can do. When thermoplastic resin particles are used, a suitable particle size exists in relation to the particle size of the porous body having mesopores. If the particle diameter of the thermoplastic resin particles is excessively large relative to the particle diameter of the porous body having mesopores, good voids cannot be formed between the porous bodies having mesopores, and the thermoplastic resin is formed during sheet formation. In some cases, a porous body having mesopores is buried in the resin particles, and a sufficient absorption / desorption function cannot be exhibited. Even if the particle diameter of the thermoplastic resin particles is excessively small, porous bodies having mesopores are in close contact with each other, and the porosity of the absorption / desorption layer is reduced. Thermoplastic resin particles having an excessively small particle size are difficult to obtain as a commercial product and have the disadvantage of being inferior in uniform mixing with a porous material having mesopores.
 熱可塑性樹脂粒子の平均粒子径は、メソ孔を有する多孔体の平均粒子径に対して、熱可塑性樹脂粒子の平均粒子径/メソ孔を有する多孔体の平均粒子径=1/8~15/1、特に1/7~8/1の範囲であることが好ましい。熱可塑性樹脂粒子の平均粒子径自体は、上記平均粒子径比を満たす範囲において任意であるが、入手し易さ、取り扱い性等の面から5~900μm程度であることが好ましい。 The average particle diameter of the thermoplastic resin particles is the average particle diameter of the thermoplastic resin particles / the average particle diameter of the porous body having mesopores = 1/8 to 15 / the average particle diameter of the porous body having mesopores. 1, particularly in the range of 1/7 to 8/1. The average particle diameter itself of the thermoplastic resin particles is arbitrary within the range satisfying the above average particle diameter ratio, but is preferably about 5 to 900 μm from the viewpoint of easy availability and handleability.
 熱可塑性樹脂粒子の平均粒子径は、レーザー回折散乱法(水分散湿式法)により求められた値である。 The average particle diameter of the thermoplastic resin particles is a value determined by a laser diffraction scattering method (water dispersion wet method).
 本発明の実施形態に係る吸・脱着材の吸・脱着層が上記の熱可塑性樹脂粒子を含む場合、吸・脱着層を構成する熱可塑性樹脂粒子とメソ孔を有する多孔体との重量比は1/4~4/1、特に1/3~3/1であることが好ましい。この範囲よりも熱可塑性樹脂粒子が少ないと、メソ孔を有する多孔体の成型性が悪く、シート状の吸・脱着層を形成しにくい。この範囲よりも熱可塑性樹脂粒子が多いと、メソ孔を有する多孔体成型時に溶融した樹脂が粒子間の空隙を埋めやすくなり、空隙率の低下を生じる。さらに、メソ孔を有する多孔体の細孔内に樹脂が入ったり、細孔を覆うことによって、吸・脱着性能が低下してしまい、吸・脱着性能に優れた吸・脱着材を得ることができない。 When the absorption / desorption layer of the absorption / desorption material according to the embodiment of the present invention includes the above-described thermoplastic resin particles, the weight ratio of the thermoplastic resin particles constituting the absorption / desorption layer and the porous body having mesopores is It is preferably 1/4 to 4/1, particularly 1/3 to 3/1. If the thermoplastic resin particles are less than this range, the moldability of the porous body having mesopores is poor and it is difficult to form a sheet-like absorption / desorption layer. When there are more thermoplastic resin particles than this range, the resin melted at the time of molding a porous body having mesopores easily fills the voids between the particles, resulting in a decrease in porosity. Furthermore, if the resin enters or covers the pores of the porous body having mesopores, the absorption / desorption performance decreases, and an absorption / desorption material with excellent absorption / desorption performance can be obtained. Can not.
(無機フィラー)
 吸・脱着層に、メソ孔を有する多孔体よりも比重の大きい無機フィラーを含有させることにより、吸・脱着材の比重を大きくして、生体液、その他の処理液中に沈み易くして、生体液、その他の処理液との濡れ性を高めることができる。このような目的で用いる無機フィラーとしては、ジルコン(ケイ酸ジルコニウム、比重4.7)、石英(比重2.7)、アルミナ(比重4.0)等の金属酸化物粒子や、ステンレス鋼、チタン合金(Ti-6Al-4V)、コバルト-クロム合金(バイタリウム、Co-Cr-Mo合金)等の金属粒子などの1種又は2種以上を用いることができる。なお、血液の凝固因子となる金属粒子の場合、生体不活性材料で表面コーティングして用いることが好ましい。
(Inorganic filler)
By including an inorganic filler having a specific gravity greater than that of the porous material having mesopores in the absorption / desorption layer, the specific gravity of the absorption / desorption material is increased, and it is easy to sink in biological fluids and other treatment liquids. The wettability with biological fluids and other treatment liquids can be improved. Examples of inorganic fillers used for such purposes include metal oxide particles such as zircon (zirconium silicate, specific gravity 4.7), quartz (specific gravity 2.7), alumina (specific gravity 4.0), stainless steel, titanium, and the like. One kind or two or more kinds of metal particles such as an alloy (Ti-6Al-4V) and a cobalt-chromium alloy (Vitalium, Co-Cr-Mo alloy) can be used. In addition, in the case of the metal particle used as the coagulation factor of blood, it is preferable to use it by surface coating with a bioinert material.
 無機フィラーの粒子サイズについては、過度に大きいと吸・脱着層の厚さに影響を及ぼし、また、通水性シート内でメソ孔を有する多孔体が動きやすくなり、粉もれにつながり、逆に、過度に小さいとメソ孔を有する多孔体の空隙を埋めやすくなり、吸・脱着性能を低下させるおそれがあることから、例えば、メソ孔を有する多孔体と同程度の大きさのものが用いられる。 If the particle size of the inorganic filler is excessively large, the thickness of the absorption / desorption layer will be affected, and the porous body having mesopores will move easily in the water-permeable sheet, leading to powder leakage, and conversely If it is excessively small, it becomes easy to fill the voids of the porous body having mesopores and the absorption / desorption performance may be lowered. For example, a material having the same size as the porous body having mesopores is used. .
 無機フィラーは、その目的に応じて、吸・脱着材が所望の比重となるように用いられるが、吸・脱着層内のメソ孔を有する多孔体の含有量を確保するうえで、その合計体積が吸・脱着層の見掛け体積に対して通常80%以下、好ましくは70%以下の体積率となるように用い、通常5%以上の体積率である。 The inorganic filler is used according to the purpose so that the adsorbent / desorbing material has a desired specific gravity. However, in order to secure the content of the porous body having mesopores in the adsorbing / desorbing layer, the total volume is used. Is usually 80% or less, preferably 70% or less of the apparent volume of the adsorption / desorption layer, and is usually 5% or more.
 吸・脱着層と通気性層とを積層させる場合には、吸・脱着層にシリカの粗大粒子を含有させることにより、この粗大粒子を後述の通水性層の表面から突出させて、突出したシリカ粒子を親水性の起点として吸・脱着材の濡れ性を高めることができる。この場合、シリカの粗大粒子の粒子径は吸・脱着層の厚みよりもわずかに大きい程度でよく、通常、吸・脱着層の厚みの1.5倍以上5倍以下である。シリカの粗大粒子を吸・脱着層に含有させる場合、その量が少な過ぎると十分な濡れ性向上効果を得ることができないが、多過ぎると吸・脱着層の成型安定性が損なわれたり、吸・脱着量が制限されたりするため、その合計の体積が、吸・脱着層の見掛け体積に対して通常80%以下であり、70%以下の体積率であることが好ましく、また通常5%以上の体積率である。 When laminating the absorption / desorption layer and the air-permeable layer, the coarse silica particles are protruded from the surface of the water-permeable layer, which will be described later, by incorporating coarse particles of silica in the absorption / desorption layer. The wettability of the adsorbing / desorbing material can be enhanced by using the particles as hydrophilic starting points. In this case, the particle diameter of the coarse silica particles may be slightly larger than the thickness of the absorption / desorption layer, and is usually 1.5 to 5 times the thickness of the absorption / desorption layer. In the case where coarse particles of silica are contained in the absorption / desorption layer, if the amount is too small, sufficient wettability improvement effect cannot be obtained. However, if the amount is too large, the molding stability of the absorption / desorption layer may be impaired, or the absorption. -Since the amount of desorption is limited, the total volume is usually 80% or less with respect to the apparent volume of the absorption / desorption layer, preferably 70% or less, and usually 5% or more. The volume ratio.
 吸・脱着層は、空隙率が10%以上であることが好ましい。吸・脱着層の空隙率が小さ過ぎると、吸・脱着層内への生体液や各種処理液の浸透効率が悪く、メソ孔を有する多孔体による優れた吸・脱着性能を十分に得ることができず、洗浄効率も劣るものとなる。空隙率は10%以上で、ある程度高いことが好ましいが、過度に高いと相対的にメソ孔を有する多孔体の割合が減ることにより吸・脱着性能が低下し、また、メソ孔を有する多孔体や熱可塑性樹脂粒子、その他の材料が少ないことにより吸・脱着層の成型性、形状保持性、機能性が劣るものとなる。従って、吸・脱着層の空隙率は通常15%以上、好ましくは20%以上、より好ましくは30%以上であり、また通常95%以下、好ましくは90%以下、より好ましくは85%以下である。 The absorption / desorption layer preferably has a porosity of 10% or more. If the porosity of the absorption / desorption layer is too small, the penetration efficiency of biological fluids and various treatment liquids into the absorption / desorption layer is poor, and excellent absorption / desorption performance with a porous body having mesopores can be sufficiently obtained. It cannot be performed and the cleaning efficiency is inferior. The porosity is preferably 10% or more and is preferably high to some extent. However, if the porosity is excessively high, the ratio of the porous body having mesopores is relatively reduced, so that the absorption / desorption performance is lowered, and the porous body having mesopores In addition, since there are few thermoplastic resin particles and other materials, the moldability, shape retention, and functionality of the absorption / desorption layer are inferior. Accordingly, the porosity of the adsorption / desorption layer is usually 15% or more, preferably 20% or more, more preferably 30% or more, and usually 95% or less, preferably 90% or less, more preferably 85% or less. .
 なお、ここで、吸・脱着層の空隙率は、例えば、メソ孔を有する多孔体と熱可塑性樹脂粒子とからなる吸・脱着層の場合、以下の方法で求められる値である。 Here, the porosity of the adsorption / desorption layer is, for example, a value obtained by the following method in the case of an adsorption / desorption layer composed of a porous body having mesopores and thermoplastic resin particles.
(吸・脱着層の空隙率)
 吸・脱着層の空隙率とは、吸・脱着層の両面に表面平滑なシートを積層したときに、そのシート間に形成される体積のうち、空隙(ただし、メソ孔を有する多孔体の細孔容積は含まない)が占める割合(百分率)をさし、吸・脱着層を構成する材料の比重及び使用重量から求めた吸・脱着層に占める構成材料の体積と、吸・脱着層の見掛け体積(後述の通水性シート間に形成される体積)から計算によって求められる。
 具体的には、12cm×12cm(面積)の吸・脱着層について、次のような方法で算出される。
 吸・脱着層体積[cm]:12×12×(吸・脱着層厚さ)
 メソ孔を有する多孔体の体積[cm]:
  (吸・脱着層重量)×(吸・脱着層構成材料中のメソ孔を有する多孔体の重量割合)/(メソ孔を有する多孔体の真比重)
 メソ孔を有する多孔体の細孔容積[cm]:
  (吸・脱着層重量)×(吸・脱着層構成材料中のメソ孔を有する多孔体の重量割合)×(メソ孔を有する多孔体の細孔容積[cm])
 熱可塑性樹脂粒子体積[cm]:
  (吸・脱着層重量)×(吸・脱着層構成材料中の熱可塑性樹脂粒子重量割合)/(熱可塑性樹脂粒子密度)
 空隙容積[cm]:
  (吸・脱着層体積[cm]-メソ孔を有する多孔体の粒子体積[cm]-メソ孔を有する多孔体の細孔容積[cm]-熱可塑性樹脂粒子体積[cm])
 吸・脱着層空隙率[%]:(空隙容積[cm])/(吸・脱着層体積[cm])×100
(Porosity of absorption / desorption layer)
The porosity of the absorption / desorption layer refers to the void (however, the fineness of the porous body having mesopores) out of the volume formed between the sheets when a smooth surface sheet is laminated on both sides of the absorption / desorption layer. The volume of the constituent material occupying the absorption / desorption layer determined from the specific gravity of the material constituting the absorption / desorption layer and the weight used, and the appearance of the absorption / desorption layer It is calculated | required by calculation from the volume (volume formed between the water-permeable sheets mentioned later).
Specifically, the absorption / desorption layer of 12 cm × 12 cm (area) is calculated by the following method.
Absorption / desorption layer volume [cm 3 ]: 12 × 12 × (absorption / desorption layer thickness)
Volume of porous body having mesopores [cm 3 ]:
(Weight of absorption / desorption layer) × (weight ratio of porous body having mesopores in the material constituting absorption / desorption layer) / (true specific gravity of porous body having mesopores)
Pore volume [cm 3 ] of a porous body having mesopores:
(Adsorption / desorption layer weight) × (weight ratio of porous body having mesopores in the constituent material of absorption / desorption layer) × (pore volume [cm 3 ] of porous body having mesopores)
Thermoplastic resin particle volume [cm 3 ]:
(Weight of absorption / desorption layer) × (weight ratio of thermoplastic resin particles in the material constituting absorption / desorption layer) / (thermoplastic resin particle density)
Void volume [cm 3 ]:
(Adsorption and desorption layer volume [cm 3] - particle volume of the porous body having mesopores [cm 3] - pore volume of the porous body having mesopores [cm 3] - thermoplastic resin particle volume [cm 3])
Absorption / desorption layer porosity [%]: (void volume [cm 3 ]) / (absorption / desorption layer volume [cm 3 ]) × 100
 吸・脱着層の厚さは、接液処理時の液の浸透性、通過性の面からは、薄い方が好ましい。従って、吸・脱着層の厚さは、層内に含まれるメソ孔を有する多孔体の平均粒子径の20倍以下であることが好ましく、10倍以下であることがより好ましく、5倍以下であることが更に好ましい。また2倍以上であることが好ましい。即ち、吸・脱着層の厚さ方向に、メソ孔を有する多孔体の層が2~5層程度形成される厚さであることが好ましい。
 例えば、吸・脱着層の厚さは、好ましくは100μm以上、より好ましくは200μm以上、また、好ましくは2000μm以下、より好ましくは1500μm以下である。
The thickness of the absorption / desorption layer is preferably thin from the viewpoint of the permeability and permeability of the liquid during the liquid contact treatment. Therefore, the thickness of the absorption / desorption layer is preferably 20 times or less, more preferably 10 times or less, and more preferably 5 times or less the average particle diameter of the porous body having mesopores contained in the layer. More preferably it is. Moreover, it is preferable that it is 2 times or more. That is, the thickness is preferably such that about 2 to 5 porous layers having mesopores are formed in the thickness direction of the absorption / desorption layer.
For example, the thickness of the absorption / desorption layer is preferably 100 μm or more, more preferably 200 μm or more, and preferably 2000 μm or less, more preferably 1500 μm or less.
<通水性層>
 本発明の実施形態に係る吸・脱着材は、通水性層を有してもよい。通水性層は、親水性、通水性に優れ、生体適合性の材料であって、取り扱い時に必要な機械的強度、耐薬品性等を満たすものであればよく、特に制限はないが、織布又は不織布を用いることが好ましい。
 織布又は不織布としては、市販のものを用いることができるが、特に安価であり、目開き調整されたものを容易に入手できる点から、通水性層としては、不織布を用いることが好ましい。
<Water-permeable layer>
The absorption / desorption material according to the embodiment of the present invention may have a water-permeable layer. The water permeable layer is not particularly limited as long as it is a material having excellent hydrophilicity, water permeability, and biocompatibility and satisfying mechanical strength, chemical resistance, etc. required for handling. Or it is preferable to use a nonwoven fabric.
Although a commercially available thing can be used as a woven fabric or a nonwoven fabric, It is preferable to use a nonwoven fabric as a water-permeable layer from the point which is especially cheap and can obtain easily the thing by which opening adjustment was carried out.
 通水性層に用いる不織布又は織布を構成する繊維としては、ポリエチレンテレフタレート、ポリトリメチレンテレフタレートなどのポリエステル繊維;ポリアクリル繊維;ポリエチレン、ポリプロピレンなどのポリオレフィン繊維;ナイロン6、ナイロン66などのポリアミド繊維のような合成繊維;レーヨン、アセテート繊維などの半合成繊維などを1種以上組み合わせたものを使用できる。これらのうち、半合成繊維、特にレーヨンは濡れ性が高い点で吸・脱着を行う際の取り扱いやすい点で好ましく、ポリオレフィン繊維は生体物質の回収率が高い点で好ましい。ポリエステル繊維は濡れ性と生体物質の回収率をバランス良く満たす点で好ましい。
 また、芯鞘構造として熱融着性を付与した繊維や、繊維を極細化、繊維断面の異形化、側面への溝や凹部の付与、繊維の多孔化などによって親水性を高めた特殊繊維や、親水性のコーティング処理を施した表面処理繊維などを用いることもできる。特に、芯鞘繊維は、後述の本発明の吸・脱着材の製造の際に、切断時に容易にヒートシールを施すことができ、好ましい。
Examples of fibers constituting the nonwoven fabric or woven fabric used in the water-permeable layer include polyester fibers such as polyethylene terephthalate and polytrimethylene terephthalate; polyacrylic fibers; polyolefin fibers such as polyethylene and polypropylene; polyamide fibers such as nylon 6 and nylon 66 Such synthetic fibers; those obtained by combining one or more semi-synthetic fibers such as rayon and acetate fibers can be used. Of these, semi-synthetic fibers, particularly rayon, are preferable because they have high wettability, and are easy to handle when desorbing and desorbing, and polyolefin fibers are preferable because of high recovery of biological materials. Polyester fibers are preferable in that they satisfy a good balance between wettability and biological material recovery.
In addition, fibers with heat-fusibility as a core-sheath structure, special fibers with increased hydrophilicity, such as ultra-fine fibers, irregular fiber cross-sections, grooves and recesses on side surfaces, and fiber porosity Further, surface-treated fibers subjected to hydrophilic coating treatment can also be used. In particular, the core-sheath fiber is preferable because it can be easily heat-sealed at the time of cutting when the absorption / desorption material of the present invention described later is produced.
 通水性層は、接液処理時の各種の液の浸透性、通過性から、目開きが大きい方が好ましいが、過度に大きいと吸・脱着層の成型安定性が劣るものとなる。
 また、通水性層の厚さについては、吸・脱着材の強度の確保、熱融着のしやすさの観点からは厚い方が好ましく、薄肉化のためには薄い方が好ましい。
 接液処理時の各種の液の浸透性、通過性、吸・脱着材の強度、取り扱い性等の面からは、通水性層は以下の条件を満たすことが好ましい。
The water-permeable layer preferably has a larger opening due to the permeability and permeability of various liquids during the liquid contact treatment, but if it is excessively large, the molding stability of the absorption / desorption layer will be inferior.
Further, the thickness of the water-permeable layer is preferably thicker from the viewpoint of securing the strength of the absorbent / desorbing material and ease of heat fusion, and thinner for thinner.
The water-permeable layer preferably satisfies the following conditions from the standpoints of the permeability, permeability, various strengths of the absorbent / desorbent, and handleability of various liquids during the liquid contact treatment.
 通水性層の平均目開きは、通常1μm以上、好ましくは10μm以上であり、また通常300μm以下、好ましくは200μm以下である。通水性層の平均目開きは、吸・脱着層内のメソ孔を有する多孔体の平均粒子径に対して通常0.1倍以上、好ましくは0.2倍以上であり、また通常1倍以下、好ましくは0.8倍以下である。 The average opening of the water-permeable layer is usually 1 μm or more, preferably 10 μm or more, and usually 300 μm or less, preferably 200 μm or less. The average opening of the water-permeable layer is usually 0.1 times or more, preferably 0.2 times or more, and usually 1 time or less with respect to the average particle diameter of the porous body having mesopores in the absorption / desorption layer. , Preferably 0.8 times or less.
 通水性層の厚さは通常50μm以上、好ましくは70μm以上、より好ましくは100μm以上であり、また通常1000μm以下、好ましくは500μm以下、より好ましくは300μm以下である。吸・脱着層内のメソ孔を有する多孔体の重量(g/m)に対して通水性層の重量(g/m)が1/10~10倍、特に1/5~5倍となるように用いることが好ましい。
 また、通水性層が不織布である場合、その目付量が通常10g/m以上、好ましくは20g/m以上、より好ましくは30g/m以上であり、通常200g/m以下、好ましくは150g/m以下、より好ましくは100g/m以下である。
The thickness of the water-permeable layer is usually 50 μm or more, preferably 70 μm or more, more preferably 100 μm or more, and usually 1000 μm or less, preferably 500 μm or less, more preferably 300 μm or less. Weight of the water-permeable layer (g / m 2) is 1/10 to 10 times the weight of the porous body having mesopores of adsorption and desorption layer (g / m 2), and in particular 1 / 5-5 times It is preferable to use it as follows.
When the water-permeable layer is a nonwoven fabric, the basis weight is usually 10 g / m 2 or more, preferably 20 g / m 2 or more, more preferably 30 g / m 2 or more, and usually 200 g / m 2 or less, preferably It is 150 g / m 2 or less, more preferably 100 g / m 2 or less.
 また、通水性層は、JIS L 1096 6.27.1 A法(フラジール法)に準じて測定した通気度が通常50cc/cm・sec以上、好ましくは70cc/cm・sec以上であり、また通常250cc/cm・sec以下、好ましくは200cc/cm・sec以下である。 The water-permeable layer has an air permeability measured according to JIS L 1096 6.27.1 A method (Fragile method) of usually 50 cc / cm 2 · sec or more, preferably 70 cc / cm 2 · sec or more, Further, it is usually 250 cc / cm 2 · sec or less, preferably 200 cc / cm 2 · sec or less.
 また、通水性層の比表面積に対して吸・脱着層内のメソ孔を有する多孔体の比表面積が通常1000倍以上、好ましくは1万倍以上であり、また通常1000万倍以下である。ここで、通水性層の比表面積とは、通水性層が織布又は不織布で構成される場合、構成する糸(繊維)の表面積の値であり、メソ孔を有する多孔体の比表面積とは粒子外表面積と細孔内表面積の合計の値であり、窒素ガスBET法により求めることができる。 Further, the specific surface area of the porous body having mesopores in the absorption / desorption layer with respect to the specific surface area of the water-permeable layer is usually 1000 times or more, preferably 10,000 times or more, and usually 10 million times or less. Here, the specific surface area of the water-permeable layer is the value of the surface area of the yarn (fiber) to be formed when the water-permeable layer is composed of a woven fabric or a non-woven fabric, and the specific surface area of the porous body having mesopores. This is the total value of the surface area outside the particle and the surface area inside the pore, and can be determined by the nitrogen gas BET method.
 通水性層が織布又は不織布で構成される場合、織布又は不織布を構成する繊維の疎水性が高く、十分な濡れ性が得られない場合には、次のような親水性向上処理を施してもよい。
(1) 織布又は不織布に、アルゴン又は酸素等のプラズマによる表面処理を施し、水酸基を導入して親水性を高める。
(2) サンドブラスト等で織布又は不織布の表面粗さを高めることで、濡れ性、親水性を高める。このブラスト処理で織布又は不織布の表面に親水性元素を打ち込み、これにより更に親水性を高めることもできる。
(3) セルロース繊維、レーヨン繊維、ポリビニルアルコール(PVA)繊維、エチレン酢酸ビニルコポリマー(EVA)繊維等の親水性繊維、或いは、酢酸ビニルやビニルアルコール等の親水性モノマーを用いた親水性共重合樹脂繊維などを、織布又は不織布を構成する繊維として、単独で、或いは、通水性シートに用いる不織布又は織布を構成する繊維として先に例示したものに加えて、これらの繊維と混合して、或いは積層して、或いは短繊維としてバインダ等を用いてシート化するなどの方法で用いる。
(4) ポリエチレングリコール、ポリ(2-ヒドロキシエチルメタクリレート)、ポリ(アクリルアミド)、スルホン化セグメントポリウレタン等の親水性基を織布又は不織布表面に物理的又は化学的に固着させる処理を行う。
(5) 織布又は不織布の表面にシリカコーティング処理を施して親水化する。このシリカコーティングは、織布又は不織布に対して、ドット状、又は線状に印刷することで部分的に行うものであってもよい。
When the water-permeable layer is composed of a woven or non-woven fabric, if the fibers constituting the woven or non-woven fabric are highly hydrophobic and sufficient wettability cannot be obtained, the following hydrophilicity improving treatment is applied. May be.
(1) A surface treatment using a plasma such as argon or oxygen is performed on a woven fabric or a non-woven fabric to introduce a hydroxyl group to enhance hydrophilicity.
(2) Improve wettability and hydrophilicity by increasing the surface roughness of the woven or non-woven fabric with sandblasting or the like. By this blasting treatment, a hydrophilic element can be implanted into the surface of the woven or non-woven fabric, thereby further improving the hydrophilicity.
(3) Hydrophilic copolymer resin using hydrophilic fibers such as cellulose fiber, rayon fiber, polyvinyl alcohol (PVA) fiber, ethylene vinyl acetate copolymer (EVA) fiber, or hydrophilic monomers such as vinyl acetate and vinyl alcohol A fiber, etc., as a fiber constituting a woven fabric or a nonwoven fabric, alone or in addition to those exemplified above as a fiber constituting a nonwoven fabric or a woven fabric used for a water-permeable sheet, mixed with these fibers, Alternatively, it is used by a method of laminating or forming a sheet using a binder or the like as a short fiber.
(4) A treatment for physically or chemically fixing hydrophilic groups such as polyethylene glycol, poly (2-hydroxyethyl methacrylate), poly (acrylamide), and sulfonated segment polyurethane to the surface of the woven or non-woven fabric is performed.
(5) The surface of the woven or non-woven fabric is subjected to a silica coating treatment to make it hydrophilic. This silica coating may be performed partially by printing dots or lines on a woven or non-woven fabric.
 通水性層の親水性の程度としては、1cm角のシートを水面に浮かすような形で水につけた時に短時間で水中に埋没する程度がよい。好ましくは1分以内、より好ましくは30秒以内に埋没する程度の親水性を有することが好ましい。また、親水性の程度を示す別な方法として、通水性層に純水の水滴を落としたときに、10秒以内にシートへの水の浸み込みが始まるものが良く、望ましくは5秒以内に水が浸み込むものがよい。 The degree of hydrophilicity of the water-permeable layer is such that when a 1 cm square sheet is immersed in water in a form that floats on the water surface, it is buried in water in a short time. The hydrophilicity is preferably such that it is buried within 1 minute, more preferably within 30 seconds. In addition, as another method for indicating the degree of hydrophilicity, when water droplets of pure water are dropped on the water-permeable layer, water starts to penetrate into the sheet within 10 seconds, preferably within 5 seconds. It should be soaked in water.
 また、生体液や各種処理液内に吸・脱着材が沈み易くするための比重調整として、通水性層に、比重の大きい材料よりなる孔明きシート(例えば、パンチングメタル)を積層したり、高比重材料を含有させたりしてもよい。 In addition, as a specific gravity adjustment to make it easier for the absorbent / desorbent material to sink in biological fluids and various processing liquids, a perforated sheet (for example, punching metal) made of a material having a high specific gravity is laminated on the water-permeable layer, A specific gravity material may be included.
 通水性層には、吸・脱着材を生体液内に浸漬した際に、夾雑物で目詰まりしたり、粘着物が付着したりすることがないことが好ましい。また、接液処理時の各種の液の浸透性、通過性の面からは、親水性に優れることが好ましい。ただし、通水性層の材質や表面処理の方式によっては、通水性層への生体物質の吸着量が多くなり過ぎ、吸・脱着層内のメソ孔を有する多孔体の細孔内への生体物質の吸着量が少なくなるおそれもあることから、表面状態を適宜調整することが好ましい。
 表面状態の調整には、例えば、抗血栓性の材料を適用するのが好ましく、抗血栓性材料としては、ヘパリン固定化コーティング材料、ウロキナーゼ固定化コーティング材料、トロンボモジェリン固定化コーティング材料、セグメント化ポリウレタンコーティング材料、合成系生体適合性コーティング材料、リン脂質吸着または固定化コーティング材料(MPCポリマー)、アルキル化セルロースコーティング材料等が挙げられる。
It is preferable that the water-permeable layer does not become clogged with contaminants or adhere to an adhesive when the absorbent / desorbent is immersed in the biological fluid. Moreover, it is preferable that it is excellent in hydrophilicity from the surface of the permeability of various liquids at the time of a liquid-contact process, and a permeability. However, depending on the material of the water-permeable layer and the surface treatment method, the amount of biological material adsorbed on the water-permeable layer is excessive, and the biological material in the pores of the porous body having mesopores in the absorption / desorption layer It is preferable to adjust the surface state as appropriate because there is a possibility that the amount of adsorbed will be reduced.
For the adjustment of the surface condition, for example, an antithrombotic material is preferably applied, and examples of the antithrombotic material include heparin-immobilized coating material, urokinase-immobilized coating material, thrombomogerin-immobilized coating material, and segmentation. Examples include polyurethane coating materials, synthetic biocompatible coating materials, phospholipid adsorption or immobilization coating materials (MPC polymers), and alkylated cellulose coating materials.
 また、疎水性となって親水性が低下するデメリットはあるものの、生体適合性に優れたものとすることができることから、ポリジメタルシロキサンなどのシリコーン材料を通水性層に用いたり、シリコーンコーティングを通水性層に施したりしてもよい。
 ポリエチレン、ポリプロピレンに代表されるポリオレフィン、ポリ四フッ化エチレンなどのフッ素樹脂は、通水性層の構成材料としても、またコーティング材料としても好ましく用いることができる。
In addition, although there is a demerit that it becomes hydrophobic and lowers hydrophilicity, it can be made excellent in biocompatibility. Therefore, a silicone material such as polydimetalsiloxane can be used for the aqueous layer or a silicone coating can be passed. It may be applied to the aqueous layer.
Fluorine resins such as polyethylene and polyolefins typified by polypropylene and polytetrafluoroethylene can be preferably used as a constituent material of the water-permeable layer and also as a coating material.
<本発明の吸・脱着材の構成>
 以下に図面を参照して本発明の吸・脱着材の具体的な構造例について説明するが、以下の説明は本発明の吸・脱着材の一例であって、本発明の吸・脱着材は何ら以下のものに限定されるものではない。
<Configuration of Absorption / Desorption Material of the Present Invention>
A specific structural example of the adsorbing / desorbing material of the present invention will be described below with reference to the drawings. The following description is an example of the absorbing / desorbing material of the present invention, and the adsorbing / desorbing material of the present invention is It is not limited to the following.
 図1は、本発明の吸・脱着材の実施の形態の一例を示す模式的な断面図である。
 図1(a)は、メソ孔を有する多孔体を含むシートの好ましい態様の一例であり、吸・脱着材1が、メソ孔を有する多孔体2がバインダ3で互いに接着したシート状の吸・脱着層4の両面に、通水性層5が積層されている。吸・脱着層4と通水性層5とは、吸・脱着層4に含まれるバインダ3により接着されている。
 吸・脱着層4の両面に、通水性層5が積層されている形態の吸・脱着材の厚さは、通常300μm以上、好ましくは500μm以上であり、通常5000μm以下、好ましくは4000μm以下、より好ましくは3000μm以下である。
FIG. 1 is a schematic cross-sectional view showing an example of an embodiment of the adsorption / desorption material of the present invention.
FIG. 1A is an example of a preferred embodiment of a sheet including a porous body having mesopores. The absorbent / desorbing material 1 is a sheet-like absorbent / desorbing material in which a porous body 2 having mesopores is bonded to each other with a binder 3. A water-permeable layer 5 is laminated on both surfaces of the desorption layer 4. The absorption / desorption layer 4 and the water-permeable layer 5 are bonded together by a binder 3 included in the absorption / desorption layer 4.
The thickness of the absorbent / desorbable material in which the water-permeable layer 5 is laminated on both surfaces of the absorbent / desorbable layer 4 is usually 300 μm or more, preferably 500 μm or more, and usually 5000 μm or less, preferably 4000 μm or less. Preferably it is 3000 micrometers or less.
 図1(a)において吸・脱着層4はメソ孔を有する多孔体2とバインダ3とで構成されているが、本発明に係る吸・脱着層4は更に前述の無機フィラーやシリカの粗大粒子を含んでいてもよい。吸・脱着層4の両面の通水性層5は、一方の通水性層と他方の通水性層とが同じ材料でも異なる材料でもよい。
 吸・脱着層4の両面に、通水性層5が積層されている構成において、吸・脱着層4はバインダ3を含んでも含まなくてもよい。
 バインダを含む場合は図1(a)に示した通り、メソ孔を有する多孔体2がバインダ3で互いに接着したシート状の吸・脱着層4を形成する。
 バインダを含まない場合は、(a-i)吸・脱着層が、バインダを含まずに成型されたメソ孔を有する多孔体の成型体である、(a-ii)吸・脱着層が、メソ孔を有する多孔体を通水性層に固定されて形成された層である、(a-iii)吸・脱着層が、メソ孔を有する多孔体が通水性層で挟持されることで層の形状を保持する、等の態様により、吸・脱着材をシートの形状としうる。
In FIG. 1 (a), the absorption / desorption layer 4 is composed of a porous body 2 having mesopores and a binder 3. May be included. The water-permeable layers 5 on both surfaces of the absorption / desorption layer 4 may be made of the same material or different materials in one water-permeable layer and the other water-permeable layer.
In the structure in which the water-permeable layer 5 is laminated on both surfaces of the absorption / desorption layer 4, the absorption / desorption layer 4 may or may not include the binder 3.
When a binder is included, a sheet-like absorption / desorption layer 4 in which porous bodies 2 having mesopores are bonded to each other with a binder 3 is formed as shown in FIG.
When the binder is not included, the (ai) absorption / desorption layer is a porous molded body having mesopores molded without the binder, and (aii) the absorption / desorption layer is a mesopore. (A-iii) Absorption / desorption layer, which is a layer formed by passing a porous body having pores to a water-permeable layer, is formed by sandwiching a porous body having mesopores between water-permeable layers. The adsorbing / desorbing material can be formed into a sheet shape by a mode such as maintaining
 (a-i)吸・脱着層が、バインダを含まずに成型されたメソ孔を有する多孔体の成型体である場合、該成型体は、例えば、メソ孔を有する多孔体を打錠成型することで得られる。吸・脱着層がバインダを含まない場合、吸・脱着層と通水性層とを、前述のバインダと同一の材料を用いて積層しても良く、融着できる材料を含む通水性層により熱融着してもよい。本実施態様は、吸・脱着層が脆くなりやすい一方で、バインダの量を低減することができ、メソ孔を有する多孔体に生体物質を含有する液を効率的に接触させることができる点で好ましい。 (Ai) When the absorption / desorption layer is a porous molded body having mesopores molded without containing a binder, the molded body, for example, compresses and molds a porous body having mesopores. Can be obtained. When the absorption / desorption layer does not contain a binder, the absorption / desorption layer and the water-permeable layer may be laminated using the same material as the binder described above, and heat fusion is performed by the water-permeable layer containing a material that can be fused. You may wear it. In this embodiment, the absorption / desorption layer is likely to be brittle, while the amount of the binder can be reduced, and the liquid containing the biological material can be efficiently brought into contact with the porous body having mesopores. preferable.
 (a-ii)吸・脱着層が、メソ孔を有する多孔体を通水性層に固定されて形成された層である場合は、吸・脱着層を形成するために、2つの通水性層の一方の層にのみメソ孔を有する多孔体を固定しても、両方の通水性層にメソ孔を有する多孔体を固定してもよい。吸・脱着材が含むメソ孔を有する多孔体の量を多くしやすい点で、両方の通水性層にメソ孔を有する多孔体を固定するのが好ましい。該固定の方法は限定されず、例えばメソ孔を有する多孔体をバインダにより通水層に接着してもよく、通水性層に融着できる材料を用いてメソ孔を有する多孔体と通水性層とを融着してもよい。本実施形態において2つの通水性層は吸・脱着層を介して接着されないため、2つの通水性層を相互に固定する必要がある。2つの通水性層の固定の位置は限定されず、例えば、2つの通水性層の周縁部同士を固定する方法や、2つの通水性層を所定の間隔で固定する方法が挙げられる。該固定の方法は限定されず、例えば接着でも熱融着でもよい。接着の場合には前述のバインダを接着剤として用いてもよい。融着する場合は、通水性層が熱融着できる材質であるのが好ましい。固定の位置は限定されないが、粉もれを抑止するためには、通水性層の周縁部を接合するのが好ましい。本実施形態によれば、メソ孔を有する多孔体の表面においてバインダと接触する面積が少なくなるため、接液処理を効率的に行うことができる点や、メソ孔を有する多孔体2が通水性層に固定されているため、粉もれが生じづらい点で好ましい。 (A-ii) In the case where the absorption / desorption layer is a layer formed by fixing a porous body having mesopores to the aqueous layer, in order to form the absorption / desorption layer, A porous body having mesopores may be fixed only to one layer, or a porous body having mesopores may be fixed to both water-permeable layers. It is preferable to fix the porous body having mesopores to both water-permeable layers in that the amount of the porous body having mesopores contained in the adsorbing / desorbing material is easily increased. The fixing method is not limited. For example, a porous body having mesopores and a water-permeable layer may be bonded to the water-permeable layer with a binder and a material that can be fused to the water-permeable layer is used. And may be fused. In this embodiment, since two water-permeable layers are not adhere | attached through an absorption / desorption layer, it is necessary to fix two water-permeable layers mutually. The fixing position of the two water-permeable layers is not limited, and examples thereof include a method of fixing the peripheral portions of the two water-permeable layers and a method of fixing the two water-permeable layers at a predetermined interval. The fixing method is not limited, and may be, for example, adhesion or heat fusion. In the case of bonding, the aforementioned binder may be used as an adhesive. In the case of fusion, the water-permeable layer is preferably made of a material that can be heat-sealed. The fixing position is not limited, but it is preferable to join the peripheral edge of the water-permeable layer in order to prevent powder leakage. According to this embodiment, since the area in contact with the binder is reduced on the surface of the porous body having mesopores, the liquid contact treatment can be efficiently performed, and the porous body 2 having mesopores is water-permeable. Since it is fixed to the layer, it is preferable in that it is difficult for the powder to leak.
 (a-iii)吸・脱着層が、メソ孔を有する多孔体が通水性層で挟持されることで層の形状を保持する場合、接液処理時にメソ孔を有する多孔体が流動し、前述のように粉もれが生じるおそれがある。通水性層の周縁部から多孔体がもれないように、2枚の通水性層の周縁部を固定した態様が好ましい。2つの通水性層の周縁部を固定する方法は限定されず、例えば接着でも融着でもよい。接着の場合には前述のバインダを接着剤として用いてもよい。2つの通水性層が所定の間隔で融着していてもよい。この場合、通水性層に熱融着できる材質を用いるのが好ましい。 (A-iii) When the absorption / desorption layer holds the shape of the layer by sandwiching the porous body having mesopores with the water-permeable layer, the porous body having mesopores flows during the liquid contact treatment, Like this, there is a risk of powder leakage. The aspect which fixed the peripheral part of the two water-permeable layers so that a porous body may not leak from the peripheral part of a water-permeable layer is preferable. The method for fixing the peripheral portions of the two water-permeable layers is not limited, and for example, adhesion or fusion may be used. In the case of bonding, the aforementioned binder may be used as an adhesive. Two water-permeable layers may be fused at a predetermined interval. In this case, it is preferable to use a material that can be heat-sealed to the water-permeable layer.
 また、接液処理時の各種の液の浸透性、通過性を確保した上で、吸・脱着層におけるメソポーラスシリカ粒子の流動性が適度なものとなるように、設計上の工夫を行うことが好ましい。
 なお、吸・脱着層4がバインダ3を含む場合であっても、メソ孔を有する多孔体2が吸・脱着層4から脱落し、粉もれが生じる場合があるため、粉もれを抑制するためには、設計上の工夫を行うことが好ましい。
 吸・脱着層4がバインダ3を含み、吸・脱着層4の両面に通水性層5が積層された図1(a)の態様は、特に吸・脱着材1からの粉もれを抑制するのに好ましい態様であり、生体物質の分析装置の安定運転を阻害しづらい点で好ましい。
In addition, it is possible to devise the design so that the fluidity of the mesoporous silica particles in the adsorption / desorption layer becomes appropriate while ensuring the permeability and permeability of various liquids during the liquid contact treatment. preferable.
Even if the absorption / desorption layer 4 includes the binder 3, the porous body 2 having mesopores may fall off from the absorption / desorption layer 4 to cause powder leakage, thereby suppressing the powder leakage. In order to do so, it is preferable to devise a design.
The embodiment of FIG. 1A in which the absorption / desorption layer 4 includes the binder 3 and the water-permeable layer 5 is laminated on both surfaces of the absorption / desorption layer 4 particularly suppresses the powder from leaking from the absorption / desorption material 1. This is a preferred embodiment, and is preferred in that it is difficult to inhibit the stable operation of the biological material analyzer.
 図1(b)は、メソ孔を有する多孔体を含む吸・脱着層と通水性層とが積層された吸・脱着材の好ましい態様の一例である。メソ孔を有する多孔体2がバインダ3で互いに接着してシート状の吸・脱着層4を形成し、吸・脱着層4の一方の面に、通水性層5が積層されている。吸・脱着層4と通水性層5とは、吸・脱着層4に含まれるバインダ3により接着されている。
 吸・脱着層4の一方の面に、通水性層5が積層されている、すなわち一の吸・脱着層と一の通水性層が積層されている場合の吸・脱着材の厚さは、通常150μm以上、好ましくは200μm以上であり、通常3000μm以下、好ましくは2000μm以下である。
 なお、通水性層の両面に吸・脱着層が積層されていてもよい。この場合、吸・脱着材の厚さは、通常250μm以上、好ましくは400μm以上であり、通常5000μm以下、好ましくは3000μm以下、より好ましくは2000μm以下である。
 図1(b)において吸・脱着層4はメソ孔を有する多孔体2とバインダ3とで構成されているが、更に、本発明に係る吸・脱着層4は前述の無機フィラーやシリカの粗大粒子を含んでいてもよい。
 吸・脱着層4の一方の面に、通水性層5が積層されている構成において、吸・脱着層4はバインダ3を含んでも含まなくてもよい。
 バインダを含む場合は図1(b)に示した通り、メソ孔を有する多孔体2がバインダ3で互いに接着したシート状の吸・脱着層4を形成する。
 バインダを含まない場合は、(b-i)吸・脱着層が、バインダを含まずに成型されたメソ孔を有する多孔体の成型体である、(b-ii)吸・脱着層が、メソ孔を有する多孔体を通水性層に固定されて形成された層である、等の態様により、吸・脱着材をシートの形状としうる。
FIG. 1B is an example of a preferred embodiment of an absorbent / desorbing material in which an absorbing / desorbing layer including a porous body having mesopores and a water-permeable layer are laminated. Porous bodies 2 having mesopores are bonded to each other with a binder 3 to form a sheet-like absorption / desorption layer 4, and a water-permeable layer 5 is laminated on one surface of the absorption / desorption layer 4. The absorption / desorption layer 4 and the water-permeable layer 5 are bonded together by a binder 3 included in the absorption / desorption layer 4.
The water-permeable layer 5 is laminated on one surface of the absorption / desorption layer 4, that is, the thickness of the absorption / desorption material when one absorption / desorption layer and one water-permeable layer are laminated, Usually, it is 150 μm or more, preferably 200 μm or more, and usually 3000 μm or less, preferably 2000 μm or less.
In addition, the absorption / desorption layer may be laminated | stacked on both surfaces of the water-permeable layer. In this case, the thickness of the absorption / desorption material is usually 250 μm or more, preferably 400 μm or more, and is usually 5000 μm or less, preferably 3000 μm or less, more preferably 2000 μm or less.
In FIG. 1 (b), the adsorption / desorption layer 4 is composed of a porous body 2 having a mesopore and a binder 3. Further, the adsorption / desorption layer 4 according to the present invention is coarse in the inorganic filler and silica described above. It may contain particles.
In the configuration in which the water-permeable layer 5 is laminated on one surface of the absorption / desorption layer 4, the absorption / desorption layer 4 may or may not include the binder 3.
When a binder is included, a sheet-like absorption / desorption layer 4 in which porous bodies 2 having mesopores are bonded to each other with a binder 3 is formed as shown in FIG.
When the binder is not included, (bi) the absorption / desorption layer is a porous molded body having mesopores molded without the binder, (b-ii) the absorption / desorption layer is a mesopore The absorbing / desorbing material can be formed into a sheet shape by an embodiment such as a layer formed by passing a porous body having pores to the aqueous layer.
 (b-i)吸・脱着層が、バインダを含まずに成型されたメソ孔を有する多孔体の成型体である場合、該成型体は例えば、メソ孔を有する多孔体を打錠成型することで得られる。吸・脱着層がバインダを含まない場合、吸・脱着層と通水性層との積層に、前述のバインダと同一の材料を用いてもよく、融着できる材料を含む通水性層により熱融着してもよい。本実施形態は、吸・脱着層が脆くなりやすい一方で、バインダの量を低減することができ、メソ孔を有する多孔体に生体物質を含有する液を効率的に接触させることができる点で好ましい。 (Bi) When the absorption / desorption layer is a porous molded body having mesopores molded without containing a binder, the molded body is formed by, for example, tableting a porous body having mesopores. It is obtained with. When the absorption / desorption layer does not contain a binder, the same material as the binder described above may be used for the lamination of the absorption / desorption layer and the water-permeable layer. May be. In the present embodiment, the absorption / desorption layer tends to be brittle, while the amount of the binder can be reduced, and the liquid containing the biological material can be efficiently brought into contact with the porous body having mesopores. preferable.
 (b-ii)吸・脱着層が、メソ孔を有する多孔体を通水性層に固定されて形成された層である場合、該固定の方法は限定されず、例えばメソ孔を有する多孔体をバインダにより通水層に接着してもよく、通水性層に融着できる材料を用いてメソ孔を有する多孔体と通水性層とを融着してもよい。本実施形態によれば、メソ孔を有する多孔体の表面においてバインダと接触する面積が少なくなるため、接液処理を効率的に行うことができる点や、メソ孔を有する多孔体2が通水性層に固定されているため、粉もれが生じづらい点で好ましい。
 吸・脱着層4がバインダ3を含み、吸・脱着層4に通水性層5が積層された図1(b)の態様は、吸・脱着材1からの粉もれを抑制しつつ、接液処理時の各種の液を吸・脱着層4に接触しやすい点で好ましい。
(B-ii) When the absorption / desorption layer is a layer formed by fixing a porous body having mesopores to the aqueous layer, the fixing method is not limited. For example, a porous body having mesopores The porous body having mesopores and the water-permeable layer may be fused using a material that can be adhered to the water-permeable layer with a binder and can be fused to the water-permeable layer. According to this embodiment, since the area in contact with the binder is reduced on the surface of the porous body having mesopores, the liquid contact treatment can be efficiently performed, and the porous body 2 having mesopores is water-permeable. Since it is fixed to the layer, it is preferable in that it is difficult for the powder to leak.
In the embodiment of FIG. 1B in which the absorption / desorption layer 4 includes the binder 3 and the water-permeable layer 5 is laminated on the absorption / desorption layer 4, the adhesion / desorption layer 1 is prevented from leaking. Various liquids at the time of the liquid treatment are preferable in that they easily come into contact with the absorption / desorption layer 4.
 図1(c)は、メソ孔を有する多孔体2とバインダ3とを含む層を有する吸・脱着材1の好ましい態様の一例であり、メソ孔を有する多孔体2がバインダ3で互いに接着してシート状の吸・脱着材1を形成している。
 吸・脱着層に、通水性層が積層されていない形態の吸・脱着材の厚さは、通常100μm以上、好ましくは200μm以上であり、通常2000μm以下、好ましくは1000μm以下である。
 図1(c)の態様は、接液処理時の各種の液を吸・脱着層4に接触しやすく、また、メソ孔を有する多孔体2以外に生体物質が付着しうる成分がバインダ3のみのため生体物質の回収率を上げやすく、また、接液処理時の各種の液を吸・脱着層4に効率的に接触できる点で好ましい。
FIG. 1 (c) is an example of a preferred embodiment of the adsorbing / desorbing material 1 having a layer including a porous body 2 having mesopores and a binder 3. The porous body 2 having mesopores adheres to each other with the binder 3. Thus, a sheet-like absorption / desorption material 1 is formed.
The thickness of the absorbing / desorbing material in a form in which the water-permeable layer is not laminated on the absorbing / desorbing layer is usually 100 μm or more, preferably 200 μm or more, and usually 2000 μm or less, preferably 1000 μm or less.
In the embodiment of FIG. 1 (c), various components at the time of the liquid contact treatment are easily brought into contact with the absorbing / desorbing layer 4, and the component to which the biological material can adhere other than the porous body 2 having mesopores is only the binder 3. Therefore, it is preferable in that the recovery rate of the biological material can be easily increased and various liquids during the liquid contact treatment can be efficiently brought into contact with the absorption / desorption layer 4.
 本発明の吸・脱着材のシートまたは積層体の形状には特に制限はなく、適用する生体液の分析装置の形態等、目的に応じて適宜決定される。通常、シートとは、厚さよりも幅および奥行が大きい形状を意味するが、本発明において、シートまたは積層体の形状は、厚さが幅および/または奥行よりも大きい形状も含む。例えば、厚さが底面の一辺の長さよりも長い直方体や、積層方向の厚さが底面の直径よりも大きい円柱であってもよく、また、積層体の厚さ、幅、および奥行が同じ立方体であってもよい。取り扱い性の点では、厚さよりも幅および奥行が大きい形状が好ましい。
 例えば、本発明の吸・脱着材1は、図2(a)に示すような、採血用スピッツ(試験管)10に挿入し、スピッツ10内で血液6と接触して使用されることから、スピッツ10の形状に合わせ、一方の端部が先端側ほど幅狭となる略長方形状であってもよい。
The shape of the sheet or laminate of the absorbent / desorbent material of the present invention is not particularly limited, and is appropriately determined according to the purpose, such as the form of the biological fluid analyzer to be applied. Usually, the sheet means a shape having a width and depth larger than the thickness, but in the present invention, the shape of the sheet or laminate includes a shape having a thickness larger than the width and / or depth. For example, it may be a rectangular parallelepiped whose thickness is longer than the length of one side of the bottom surface, a cylinder whose thickness in the stacking direction is larger than the diameter of the bottom surface, or a cube having the same thickness, width, and depth. It may be. From the viewpoint of handleability, a shape having a larger width and depth than thickness is preferable.
For example, the suction / desorption material 1 of the present invention is inserted into a blood collection spitz (test tube) 10 as shown in FIG. 2A and used in contact with the blood 6 in the spitz 10. In accordance with the shape of the Spitz 10, a substantially rectangular shape in which one end portion becomes narrower toward the tip end side may be used.
 また、このような吸・脱着材において、処理液の通液性を高めるために、図2(b)に示すように、厚さ方向に透孔1aを形成した吸・脱着材1A、図2(c)に示すように、両側辺部に切込1bを入れた吸・脱着材1Bとしてもよい。 Further, in such an adsorbing / desorbing material, in order to enhance the liquid permeability of the processing liquid, as shown in FIG. 2B, the absorbing / desorbing material 1A having a through hole 1a in the thickness direction, as shown in FIG. As shown to (c), it is good also as the absorption / desorption material 1B which put the cut 1b in the both sides | edges.
 また、スピッツ内に挿入できる吸・脱着材シート量を大きくして吸・脱着面積を増やすために、図2(d)に示すように、先端側を蛇腹状にプリーツ加工した吸・脱着材1Cとしてもよい。 Further, in order to increase the amount of the suction / desorption material sheet that can be inserted into the spitz and increase the suction / desorption area, as shown in FIG. It is good.
 更に、吸・脱着材の小片1Dをネット7内に入れ、ティーバッグのように吊り紐8等で吊り下げて使用する構成としてもよい。 Furthermore, a configuration may be adopted in which a small piece 1D of the absorbent / desorbing material is placed in the net 7 and suspended by a hanging strap 8 or the like like a tea bag.
 なお、吸・脱着材は、例えば、以下に説明する製造方法で製造することができるが、吸・脱着層内のメソ孔を有する多孔体の脱落を確実に防止するために、吸・脱着層の両面に設けられる2枚の通水性シートの周縁を吸・脱着層の周縁よりも外側に延出させて、延出部を互いにヒートシール等で熱融着させることにより、後掲の図3(e)に示されるように、吸・脱着材26の全周縁部において、通水性層22と通水性層24の端縁部が密着されて密閉袋状とされていることが好ましい。この周縁部における通水性層同士の熱融着部の幅(図3(e)のLの長さ)は、十分な熱融着強度を確実した上で、吸・脱着材面積に対する吸・脱着層面積の割合を大きくして吸・脱着効率を高める観点から50μm以上であることが好ましく、また2000μm以下であることが好ましい。 The adsorbing / desorbing material can be manufactured, for example, by the manufacturing method described below. In order to reliably prevent the porous body having mesopores in the absorbing / desorbing layer from falling off, the adsorbing / desorbing layer is used. 3 by extending the periphery of two water-permeable sheets provided on both sides of the sheet to the outside of the periphery of the absorbing / desorbing layer and heat-sealing the extended portions by heat sealing or the like. As shown in (e), it is preferable that the edges of the water-permeable layer 22 and the water-permeable layer 24 are in close contact with each other at the entire peripheral edge portion of the absorbent / desorbable material 26 to form a sealed bag. The width of the heat-sealed portion between the water-permeable layers at the peripheral edge (the length L in FIG. 3 (e)) ensures sufficient heat-sealing strength, and absorbs / desorbs the area of the absorbing / desorbing material. From the viewpoint of increasing the layer area ratio and increasing the absorption / desorption efficiency, it is preferably 50 μm or more, and more preferably 2000 μm or less.
<吸・脱着材の製造方法>
 吸・脱着材の製造方法は限定されず、例えば次のようにして吸・脱着材を製造することができる。
 まず、図3(a)(斜視図)のように、所望のパターンに孔開き加工を施したマスク21を準備し、このマスク21を図3(b)(断面図)のように通水性層22の上方に設置し、この上からメソ孔を有する多孔体、例えばメソポーラスシリカ粒子を散布して、通水性層22上にマスク21の透孔21aのパターン形状にメソポーラスシリカ粒子層23を形成する。次いで、図3(c)(断面図)に示すように、この上に通水性層24を載せて、通水性層21/メソポーラスシリカ粒子層23/通水性層24の積層体25とする。次いで、図3(d)(平面図)に一点鎖線で示すように、得られた積層体25のメソポーラスシリカ粒子層23間を加熱しながら切断することにより、下側の通水性層22と上側の通水性層24とを熱融着すると共に切断して、図3(e)(断面図)の通り、吸・脱着層としてメソポーラスシリカ粒子23Aを含む所望の形状のシート状の吸・脱着材26を得る。更にプリーツ加工を施すことにより、図2(d)に示す吸・脱着材1Cを得ることができる。
 また、このように、加熱と切断とを同時に行う方法の他、加熱により熱融着し、その後常温に戻してから切断する方法も好適に採用される。
<Manufacturing method of absorption / desorption material>
The production method of the adsorbing / desorbing material is not limited. For example, the adsorbing / desorbing material can be produced as follows.
First, as shown in FIG. 3A (perspective view), a mask 21 in which a desired pattern is perforated is prepared, and the mask 21 is formed as a water-permeable layer as shown in FIG. 3B (cross-sectional view). A mesoporous silica particle layer 23 is formed in a pattern shape of the through holes 21a of the mask 21 on the water-permeable layer 22 by spreading a porous body having mesopores, for example, mesoporous silica particles, from above. . Next, as shown in FIG. 3C (cross-sectional view), the water-permeable layer 24 is placed thereon to form a laminate 25 of the water-permeable layer 21 / mesoporous silica particle layer 23 / water-permeable layer 24. Next, as shown by a one-dot chain line in FIG. 3D (plan view), by cutting between the mesoporous silica particle layers 23 of the obtained laminate 25 while heating, the lower water-permeable layer 22 and the upper water-permeable layer 22 are separated from each other. The water-permeable layer 24 is thermally fused and cut, and as shown in FIG. 3E (cross-sectional view), a sheet-like absorbent / desorbing material having a desired shape including the mesoporous silica particles 23A as the absorbing / desorbing layer. 26 is obtained. Further, by performing pleating, an absorbent / desorbing material 1C shown in FIG. 2 (d) can be obtained.
In addition to the method of heating and cutting at the same time as described above, a method of performing heat fusion by heating and then returning to room temperature and then cutting is suitably employed.
 吸・脱着層にメソ孔を有する多孔体と共に前述の無機フィラーやシリカの粗大粒子を含有させる場合は、上記のメソ孔を有する多孔体の散布時に、メソ孔を有する多孔体と無機フィラー及び/又はシリカの粗大粒子の混合物を散布すればよい。 When the above-mentioned inorganic filler and silica coarse particles are contained together with the porous material having mesopores in the adsorption / desorption layer, the porous material having mesopores and the inorganic filler and / or Alternatively, a mixture of coarse silica particles may be sprayed.
 また、吸・脱着層にメソ孔を有する多孔体と前述のバインダを含有させる場合は、上述のメソ孔を有する多孔体の散布時に、メソ孔を有する多孔体と例えばバインダとして熱可塑性樹脂粒子との混合物を散布し、上記と同様に積層体25とする。この積層体25をホットプレス、加熱ロール、加熱ベルトなどにより加熱して、熱可塑性樹脂の溶融でメソ孔を有する多孔体同士及びメソ孔を有する多孔体と通水性層とを接着一体化した後、上記と同様に切断する。 In addition, when the porous body having mesopores and the above-mentioned binder are included in the absorption / desorption layer, the porous body having mesopores and, for example, thermoplastic resin particles as a binder when spraying the porous body having the above-mentioned mesopores. A mixture 25 is sprayed to form a laminate 25 as described above. After this laminated body 25 is heated by a hot press, a heating roll, a heating belt or the like, the porous bodies having mesopores and the porous body having mesopores and the water-permeable layer are bonded and integrated by melting the thermoplastic resin. Then cut as above.
 このような吸・脱着層の製造工程は、ベルト上に送り出した通水性層上に、マスクを介してメソ孔を有する多孔体と必要に応じバインダなどとの混合物を散布し、その上に別途送り出した通水性層を重ねて加熱、切断する連続工程で実施することができる。 In the manufacturing process of such an absorption / desorption layer, a mixture of a porous body having mesopores and a binder as needed is sprayed on a water-permeable layer sent out on a belt through a mask, and separately on the mixture. It can implement in the continuous process which piles up the water-permeable layer sent out and heats and cut | disconnects.
[生体物質の精製キット]
 本発明の吸・脱着材は、生体物質を含有する液からの生体物質の吸・脱着に使用できる。従って、例えば生体物質を含有する液を保持するための容器の内部に吸・脱着材を格納し、生体物質の精製キットとすることができる。
 生体物質の精製キットは、吸・脱着材と前記生体物質を含有する液を保持しうる容器とを含めばよく、使用時に生体物質を含有する液を保持するための容器の内部に吸・脱着材を簡便に格納(挿入)して使用すればよい。
[Biological material purification kit]
The absorption / desorption material of the present invention can be used for absorption / desorption of a biological material from a liquid containing the biological material. Therefore, for example, an absorbent / desorbing material can be stored in a container for holding a liquid containing a biological material to obtain a biological material purification kit.
The biological material purification kit may include an absorption / desorption material and a container capable of holding the liquid containing the biological material, and the absorption / desorption is performed inside the container for holding the liquid containing the biological material during use. The material may be simply stored (inserted) for use.
 容器の材質は限定されないが、生体物質の吸・脱着操作を実施するために透明であることが好ましく、樹脂やガラスが好適に例示される。一方で、生体物質生体物質の光による分解を防ぐ目的で、有色の容器であってもよい。
 容器の容積は限定されないが、通常0.1ml以上、好ましくは0.5ml以上であって、上限は限定されないが、通常1000L以下、好ましくは100L以下、より好ましくは10L以下である。目的に応じて任意の容積を選択できる。
 容器の形状は限定されないが、容器の形状と吸・脱着材の形状とが、効率的に接液処理ができる形状であることが好ましい。
 生体物質の分析に用いる場合、容器の例として試験管、中でもマイクロチューブが好適に挙げられる。
Although the material of the container is not limited, it is preferably transparent in order to carry out a biological material absorption / desorption operation, and resin and glass are preferably exemplified. On the other hand, a colored container may be used for the purpose of preventing the biological material from being decomposed by light.
The volume of the container is not limited, but is usually 0.1 ml or more, preferably 0.5 ml or more, and the upper limit is not limited, but is usually 1000 L or less, preferably 100 L or less, more preferably 10 L or less. Any volume can be selected according to the purpose.
Although the shape of the container is not limited, it is preferable that the shape of the container and the shape of the adsorbing / desorbing material are shapes that can efficiently perform the liquid contact treatment.
When used for analysis of biological materials, examples of the container include a test tube, particularly a microtube.
[生体物質の製造方法・生体物質の分離方法]
 本発明の実施形態に係る吸・脱着材は、生体物質を含有する液から生体物質を吸・脱着して分離する公知の方法に適用できる。例えば本発明の実施形態に係る吸・脱着材を、生体物質を含有する液に接触させ、メソ孔を有する多孔体のメソ孔内に生体物質を選択的に吸着させた後、吸・脱着剤を洗浄し、生体物質を脱着させることで生体物質を得ることができる。
[Production method of biological material / Separation method of biological material]
The absorption / desorption material according to the embodiment of the present invention can be applied to a known method of absorbing / desorbing and separating a biological substance from a liquid containing the biological substance. For example, the adsorbing / desorbing material according to the embodiment of the present invention is brought into contact with a liquid containing a biological material, and the biological material is selectively adsorbed in the mesopores of the porous body having mesopores, and then the absorbing / desorbing agent. The biological material can be obtained by washing and desorbing the biological material.
 例えば生体液、具体的には血液からペプチドを分離する場合、吸・脱着材を、血液または血液を処理して得られる血漿に浸漬させるなどして接触させる。吸・脱着材を接触させる液は、目的である生体物質以外の不純物の含有量が少ない方が好ましく、不純物の除去には公知の方法を用いることができる。
 血液または血漿中のペプチドを吸・脱着層内のメソ孔を有する多孔体のメソ孔内に選択的に吸着させた後、この吸・脱着材を引き上げ、特許文献1に記載されるように、水洗した後、酸性緩衝液で処理してメソ孔を有する多孔体の外面に吸着している蛋白質や長鎖ペプチドを剥離除去し、次いでアセトニトリルを含むペプチド回収用溶媒で処理することにより、多孔体のメソ孔内に吸着しているペプチド(短鎖ペプチド)を脱着させることで、生体液からペプチドを分離回収して、高純度ペプチドを製造することができる。
For example, when separating a peptide from a biological fluid, specifically blood, the absorption / desorption material is brought into contact with the blood or plasma obtained by processing the blood. The liquid with which the adsorbing / desorbing material is brought into contact preferably has a small content of impurities other than the target biological substance, and known methods can be used for removing the impurities.
After selectively adsorbing peptides in blood or plasma into mesopores of a porous body having mesopores in the adsorption / desorption layer, the adsorption / desorption material is pulled up, as described in Patent Document 1, After washing with water, the porous body is treated with an acidic buffer solution to peel and remove proteins and long-chain peptides adsorbed on the outer surface of the porous body having mesopores, and then treated with a peptide recovery solvent containing acetonitrile. By desorbing the peptide (short chain peptide) adsorbed in the mesopores, the peptide can be separated and recovered from the biological fluid to produce a high purity peptide.
 本発明の実施形態に係る吸・脱着材を用いたペプチドの分離方法は、血液検査、ペプチド分析に有効であり、分析装置による自動化で容易かつ効率的に、高回収率で生体液からペプチドを分離回収して高精度な分析を可能とする。このため、癌や肝炎、その他の疾病の早期発見・診断に有用である。また、糖蛋白、糖ペプチドの回収、分析にも有効に適用することができる。 The peptide separation method using the adsorbent / desorbent according to the embodiment of the present invention is effective for blood tests and peptide analysis, and easily and efficiently automates the analysis of the peptide from the biological fluid with a high recovery rate. Separation and collection enable high-precision analysis. For this reason, it is useful for early detection and diagnosis of cancer, hepatitis, and other diseases. It can also be effectively applied to the recovery and analysis of glycoproteins and glycopeptides.
 また、本発明の実施形態に係る吸・脱着材は、高純度ペプチドを製造することができることから、このような検査目的以外にも、生活習慣病予防、血圧低下・安定化、脂質低下・安定化、アンチエイジングなどの作用効果を奏するサプリメントの製造等に有用である。 In addition, since the absorption / desorption material according to the embodiment of the present invention can produce a high-purity peptide, in addition to such test purposes, lifestyle-related disease prevention, blood pressure reduction / stabilization, lipid reduction / stability This is useful for the production of supplements that have effects such as aging and anti-aging.
 以下に実施例を挙げて、本発明をより具体的に説明する。
[実施例1]
 メソ孔を有する多孔体、バインダ、通水性層として以下のものを用いた。
<メソ孔を有する多孔体:メソポーラスシリカ粒子>
日本化成社製「メソピュア」
粒子径分布:70~600μm
平均粒子径:250μm
形状:破砕状
細孔径:4nm
細孔容積:0.7ml/g
比表面積:730m/g
The present invention will be described more specifically with reference to the following examples.
[Example 1]
The following were used as a porous body having mesopores, a binder, and a water-permeable layer.
<Porous body having mesopores: mesoporous silica particles>
“Meso Pure” manufactured by Nippon Kasei Co., Ltd.
Particle size distribution: 70-600μm
Average particle size: 250 μm
Shape: Crushed pore size: 4 nm
Pore volume: 0.7 ml / g
Specific surface area: 730 m 2 / g
<バインダ:熱可塑性樹脂粒子>
EVA(エチレン酢酸ビニル共重合体)
吸水率:0.09%
水接触角:91°
MFR:70g/10min
融点:97℃
平均粒子径:40μm
<Binder: Thermoplastic resin particles>
EVA (ethylene vinyl acetate copolymer)
Water absorption rate: 0.09%
Water contact angle: 91 °
MFR: 70g / 10min
Melting point: 97 ° C
Average particle size: 40 μm
<通水性層>
(株)ユウホウ製不織布「ZL4035」
構成繊維:レーヨン30%/ポリエステル70%繊維
平均目開き:60μm
厚さ:220μm
目付:50g/m
繊維密度:152.3kg/m
比表面積:0.0003m/g
<Water-permeable layer>
Nonwoven fabric “ZL4035”
Constituent fiber: 30% rayon / 70% polyester Fiber average opening: 60 μm
Thickness: 220 μm
Per unit weight: 50 g / m 2
Fiber density: 152.3 kg / m 2
Specific surface area: 0.0003 m 2 / g
 メソポーラスシリカ/バインダの重量比が7/3になるように、混合容器に仕込み、よく混合して混合粉体を得た。得られた混合粉体を、メソポーラスシリカ目付量が1000g/mとなるように、通水性層の上に均一に載せ、更にその上から通水性層を被せ、サンドウィッチ構造体とした。
 得られたサンドウィッチ構造体を、卓上テストプレス機(株式会社神藤金属工業所製)を用いて、プレス圧0.5MPa、プレス温度110℃、プレス時間4分間で熱圧着し、成型シートを作製した。
 作製した成型シートから、メソポーラスシリカ25mg相当分を切り出し、成型体サンプル1とした。
The mixed powder was obtained by mixing in a mixing container and mixing well so that the weight ratio of mesoporous silica / binder would be 7/3. The obtained mixed powder was uniformly placed on the water-permeable layer so that the basis weight of mesoporous silica was 1000 g / m 2, and the water-permeable layer was further covered thereon to form a sandwich structure.
The obtained sandwich structure was thermocompression-bonded at a press pressure of 0.5 MPa, a press temperature of 110 ° C., and a press time of 4 minutes using a desktop test press machine (manufactured by Shinto Metal Industry Co., Ltd.) to produce a molded sheet. .
A portion corresponding to 25 mg of mesoporous silica was cut out from the formed molded sheet, and a molded body sample 1 was obtained.
[試験例1]
<ペプチド溶液の調製> 
 ペプチドには、和光純薬工業株式会社製 ACTH Human 1-24 型番4109-v 0.5mg入りを使用した。その試薬瓶の中に25μLの超純水を入れ、その液滴内にペプチドを全て溶解し、ペプチド溶液を調製した。
[Test Example 1]
<Preparation of peptide solution>
The peptide used was 0.5 mg of ACTH Human 1-24 Model No. 4109-v manufactured by Wako Pure Chemical Industries, Ltd. 25 μL of ultrapure water was placed in the reagent bottle, and all of the peptide was dissolved in the droplet to prepare a peptide solution.
<ペプチドの定量方法>
 ペプチドの定量方法について、以下に示す。
 ペプチドの定量には、下記のLC/MS分析計を用いて、得られたクロマトグラムのペプチドのピーク面積比で評価を行った。
LC/MS測定機器;
LCシステム:アジレント・テクノロジー株式会社製Agilent1200
カラム:インタクト株式会社製Imtakt Presto FT-C18 4.6mm×30mm
質量分析計:アジレント・テクノロジー株式会社製 Agilent LC/MS 6130
<Method for quantifying peptides>
The peptide quantification method is shown below.
For peptide quantification, the following LC / MS analyzer was used to evaluate the peptide peak area ratio in the obtained chromatogram.
LC / MS measuring instrument;
LC system: Agilent 1200 manufactured by Agilent Technologies
Column: Imtakt Presto FT-C18 manufactured by Intact Corporation 4.6 mm × 30 mm
Mass spectrometer: Agilent LC / MS 6130 manufactured by Agilent Technologies, Inc.
 実施例1で得られた成型体サンプル1を、容積1.5mlのエッペンチューブに入れ、更に、この中に上記調製したペプチド溶液を全て添加した。
 このエッペンチューブを、ボルテックスミキサー(アズワン株式会社 型式VM-96B)を用い、回転数1500rpmで1時間攪拌し、ペプチド溶液を成型体サンプル1に吸着させた。
 その後、エッペンチューブから成型体サンプル1を取り出し、1mlのピペットチップの中に移した後、ピペットチップを定量ピペットに取り付けた。成型体サンプル1を内包したピペットチップ内に超純水を1ml吸い上げた後、吐出して水を排出し、水洗を実施した。この水洗作業を5回繰り返した。
 次に、和光純薬工業株式会社製の0.1mol/L グリシン-塩酸緩衝液(pH2.2)を1ml吸い上げた後、吐出して緩衝液を排出し、緩衝液による洗浄を実施した。この洗浄作業を5回、繰り返した。この水洗及び酸性緩衝液で処理することにより、シリカ粒子の外面に吸着しているペプチドを剥離除去した。
The molded body sample 1 obtained in Example 1 was placed in an Eppendorf tube having a volume of 1.5 ml, and all the peptide solutions prepared above were further added thereto.
The Eppendorf tube was stirred for 1 hour at a rotation speed of 1500 rpm using a vortex mixer (As One Corporation model VM-96B), and the peptide solution was adsorbed to the molded body sample 1.
Thereafter, the molded body sample 1 was taken out from the Eppendorf tube and transferred into a 1 ml pipette tip, and then the pipette tip was attached to the quantitative pipette. After 1 ml of ultrapure water was sucked into the pipette tip containing the molded body sample 1, it was discharged to discharge the water and washed with water. This washing operation was repeated 5 times.
Next, 1 ml of 0.1 mol / L glycine-hydrochloric acid buffer solution (pH 2.2) manufactured by Wako Pure Chemical Industries, Ltd. was sucked up and then discharged to discharge the buffer solution, followed by washing with the buffer solution. This washing operation was repeated 5 times. The peptide adsorbed on the outer surface of the silica particles was peeled and removed by treatment with this water washing and acidic buffer solution.
 その後、ピペットチップを定量ピペットから取り外し、ピペットチップ内にある成型体サンプル1を取り出し、容積1.5mlのエッペンチューブ内に移した。そのエッペンチューブに、和光純薬工業株式会社製の0.1vol%トリフルオロ酢酸-アセトニトリル溶液を1ml添加し、ボルテックスミキサー(回転数1500rpm)による攪拌を、30秒間実施した。
 その後、室温で1時間放置した後、ピンセットで成型体サンプル1を取り出して、残りの残液を分析サンプル1とした。この操作によって、シリカのメソ孔内に吸着しているペプチドを脱離、溶出させて回収した。
 この分析サンプル1を上述のペプチド定量方法によって定量した。結果を表1に示す。
Thereafter, the pipette tip was removed from the quantitative pipette, and the molded body sample 1 in the pipette tip was taken out and transferred into an Eppendorf tube having a volume of 1.5 ml. 1 ml of a 0.1 vol% trifluoroacetic acid-acetonitrile solution manufactured by Wako Pure Chemical Industries, Ltd. was added to the Eppendorf tube, and stirring with a vortex mixer (rotation speed: 1500 rpm) was performed for 30 seconds.
Then, after standing at room temperature for 1 hour, the molded body sample 1 was taken out with tweezers, and the remaining liquid was used as analysis sample 1. By this operation, the peptide adsorbed in the mesopores of silica was desorbed and eluted to be recovered.
This analysis sample 1 was quantified by the peptide quantification method described above. The results are shown in Table 1.
[比較例1]
 実施例1で用いたメソポーラスシリカを25mg秤量し、容積1.5mlのエッペンチューブに入れ、この中に上記ペプチド溶液を添加した。
 このエッペンチューブを、ボルテックスミキサー(アズワン株式会社 型式VM-96B)を用い、回転数1500rpmで1時間攪拌し、ペプチド溶液をメソポーラスシリカに吸着させた。
 その後、エッペンチューブ内に、超純水1mlを添加後、前述のボルテックスミキサー(回転数1500rpm)を用いて、30秒間攪拌した。その後、そのエッペンチューブを遠心分離機(CHIBITAN-R メルク株式会社製)を用い、10分間遠心分離を実施した。その後、上澄みを除去した後に超純水を1ml添加し、前述のボルテックスミキサーによる攪拌、及び遠心分離を3回繰り返した。
[Comparative Example 1]
25 mg of the mesoporous silica used in Example 1 was weighed and placed in an Eppendorf tube having a volume of 1.5 ml, and the peptide solution was added thereto.
The Eppendorf tube was stirred for 1 hour at a rotation speed of 1500 rpm using a vortex mixer (As One Corporation model VM-96B) to adsorb the peptide solution onto mesoporous silica.
Thereafter, 1 ml of ultrapure water was added to the Eppendorf tube, and the mixture was stirred for 30 seconds using the vortex mixer (rotation number: 1500 rpm). Thereafter, the Eppendorf tube was centrifuged for 10 minutes using a centrifuge (manufactured by CHIBITAN-R Merck). Thereafter, after removing the supernatant, 1 ml of ultrapure water was added, and the above-described vortex mixer stirring and centrifugation were repeated three times.
 その後、和光純薬工業株式会社製の0.1mol/L グリシン-塩酸緩衝液(pH2.2)を1ml添加し、前述の超純水添加時と同様に、ボルテックスミキサーによる攪拌、及び遠心分離を3回繰り返した。この水洗及び酸性緩衝液で処理することにより、シリカ粒子の外面に吸着しているペプチドを剥離除去した。
 次に、和光純薬工業株式会社製の0.1vol%トリフルオロ酢酸-アセトニトリル溶液を1ml添加し、ボルテックスミキサー(回転数1500rpm)による攪拌を、30秒間実施した。
 その後、室温で1時間放置し、前述の遠心分離機で10分間遠心分離を実施し、その上澄みを回収して分析サンプル1´を得た。この操作によって、シリカのメソ孔内に吸着しているペプチドを脱離、溶出させて回収した。
 この分析サンプル1´を上述のペプチド定量方法によって定量した。結果を表1に示す。
Thereafter, 1 ml of 0.1 mol / L glycine-hydrochloric acid buffer (pH 2.2) manufactured by Wako Pure Chemical Industries, Ltd. was added, and the mixture was stirred and centrifuged with a vortex mixer in the same manner as when adding ultrapure water. Repeated 3 times. The peptide adsorbed on the outer surface of the silica particles was peeled and removed by treatment with this water washing and acidic buffer solution.
Next, 1 ml of 0.1 vol% trifluoroacetic acid-acetonitrile solution manufactured by Wako Pure Chemical Industries, Ltd. was added, and stirring with a vortex mixer (rotation speed: 1500 rpm) was performed for 30 seconds.
Thereafter, the sample was allowed to stand at room temperature for 1 hour, centrifuged for 10 minutes with the above-mentioned centrifuge, and the supernatant was collected to obtain an analytical sample 1 ′. By this operation, the peptide adsorbed in the mesopores of silica was desorbed and eluted to be recovered.
This analysis sample 1 ′ was quantified by the above-described peptide quantification method. The results are shown in Table 1.
[比較例2]
 以下に示すメソポーラスシリカ粒子を用いた以外は、比較例1と同様にしてペプチドの吸・脱着評価を行った。結果を表1に示す。
<メソ孔を有する多孔体:メソポーラスシリカ粒子>
日本化成社製「メソピュア」
粒子径分布:1~10μm
平均粒子径:5μm
形状:微粉状
細孔径:4nm
細孔容積:0.6ml/g
比表面積:720m/g
[Comparative Example 2]
Peptide absorption / desorption evaluation was performed in the same manner as in Comparative Example 1 except that the mesoporous silica particles shown below were used. The results are shown in Table 1.
<Porous body having mesopores: mesoporous silica particles>
“Meso Pure” manufactured by Nippon Kasei Co., Ltd.
Particle size distribution: 1-10μm
Average particle size: 5 μm
Shape: Fine powder pore size: 4 nm
Pore volume: 0.6 ml / g
Specific surface area: 720 m 2 / g
[実施例2]
 以下に示す通水性層を用いた以外は、実施例1と同様に成型体サンプル2を作製し、分析サンプル2を得た。この分析サンプル2を上述のペプチド定量方法によって定量した。結果を表1に示す。
<通水性層>
株式会社クラレ製不織布「TM022D」
構成繊維:ポリプロピレン繊維
厚さ:188μm
目付:23g/m
[Example 2]
A molded body sample 2 was prepared in the same manner as in Example 1 except that the water-permeable layer shown below was used, and an analytical sample 2 was obtained. This analytical sample 2 was quantified by the peptide quantification method described above. The results are shown in Table 1.
<Water-permeable layer>
Non-woven fabric “TM022D” manufactured by Kuraray Co., Ltd.
Constituent fiber: Polypropylene fiber thickness: 188 μm
Weight per unit: 23 g / m 2
[実施例3]
 以下に示すメソポーラスシリカを用いた以外は、実施例1と同様に成型体サンプル3を作製し、分析サンプル3を得た。この分析サンプル3を上述のペプチド定量方法によって定量した。結果を表1に示す。
<メソ孔を有する多孔体:シリカゲル>
富士シリシア化学株式会社製「キャリアクトG-6」
粒径分布:45~150μm
形状:破砕状
細孔径:6nm
細孔容積:0.8ml/g
比表面積:560m/g
[Example 3]
A molded body sample 3 was prepared in the same manner as in Example 1 except that the mesoporous silica shown below was used, and an analytical sample 3 was obtained. This analysis sample 3 was quantified by the peptide quantification method described above. The results are shown in Table 1.
<Porous body having mesopores: silica gel>
“Carriert G-6” manufactured by Fuji Silysia Chemical Ltd.
Particle size distribution: 45 to 150 μm
Shape: Crushed pore size: 6 nm
Pore volume: 0.8ml / g
Specific surface area: 560 m 2 / g
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
 比較例1と実施例1との対比より、吸・脱着材を粉体で使用するよりも、シート状である本発明の吸・脱着材を用いることにより、ペプチドの検出量が増加することが示されている。また、実施例1と実施例2との対比により、通水性層としてPP(ポリプロピレン)を用いた方がペプチドの回収量が多いことがわかる。
 また、メソ孔を有する多孔体としてシリカゲルを用いた実施例3は、メソポーラスシリカを用いた実施例1よりもペプチドの検出量が多い。多孔体の種類が異なるため、直接の対比はできないものの、実施例3の多孔体は実施例1の多孔体と比較して粒径が小さい。多孔体は粒径が小さい方がペプチド含有液に接触する表面積が大きいため、ペプチドの吸・脱着に寄与しうる多孔体の体積が大きくなり、ペプチドの回収量が多いと考えられる。
From the comparison between Comparative Example 1 and Example 1, the use of the adsorbing / desorbing material of the present invention in the form of a sheet increases the amount of peptide detected rather than using the adsorbing / desorbing material in powder form. It is shown. Moreover, it is clear from the comparison between Example 1 and Example 2 that the amount of peptide recovered is larger when PP (polypropylene) is used as the water-permeable layer.
Further, Example 3 using silica gel as a porous material having mesopores has a larger amount of peptide detected than Example 1 using mesoporous silica. Since the types of porous bodies are different, direct comparison is not possible, but the porous body of Example 3 has a smaller particle size than the porous body of Example 1. Since the porous body has a larger surface area that comes into contact with the peptide-containing solution when the particle size is smaller, the volume of the porous body that can contribute to the absorption and desorption of the peptide increases, and it is considered that the recovered amount of peptide is large.
[実施例4]
 通水性層の厚さがペプチドの回収量に及ぼす影響を検討するためのモデル実験を行った。通水性層に用いた不織布を、成型体の両面と同面積の大きさに切り取り、成型体サンプルと一緒に試験を行った以外は、実施例1と同様にして分析サンプル4を得た。この分析サンプル4を上述のペプチド定量方法によって定量した。結果を表2に示す。
[Example 4]
A model experiment was conducted to examine the effect of the thickness of the water-permeable layer on the amount of peptide recovered. An analysis sample 4 was obtained in the same manner as in Example 1 except that the nonwoven fabric used for the water-permeable layer was cut into a size having the same area as both surfaces of the molded body and tested together with the molded body sample. This analytical sample 4 was quantified by the peptide quantification method described above. The results are shown in Table 2.
[実施例5]
 通水性層に用いた不織布を、成型体の片面と同面積の大きさに切り取り、成型体サンプルと一緒に試験を行った以外は、実施例1と同様にして分析サンプル5を得た。この分析サンプル5を上述のペプチド定量方法によって定量した。結果を表2に示す。
[Example 5]
An analysis sample 5 was obtained in the same manner as in Example 1 except that the nonwoven fabric used for the water-permeable layer was cut into a size having the same area as that of one side of the molded body and tested together with the molded body sample. This analytical sample 5 was quantified by the peptide quantification method described above. The results are shown in Table 2.
[実施例6]
 以下に示すメソポーラスシリカを用いた以外は、実施例1と同様に成型体サンプル5を作製し、分析サンプル6を得た。この分析サンプル6を上述のペプチド定量方法によって定量した。結果を表2に示す。
<メソ孔を有する多孔体:メソポーラスシリカ粒子>
 実施例1で用いた日本化成社製「メソピュア」を分級して以下の粒径分布および平均粒子径を有する多孔体を得た。
粒径分布:>425μm
平均粒子径:566μm
形状:破砕状
細孔径:4nm
細孔容積:0.7ml/g
比表面積:730m/g
[Example 6]
A molded body sample 5 was produced in the same manner as in Example 1 except that the mesoporous silica shown below was used, and an analytical sample 6 was obtained. This analytical sample 6 was quantified by the peptide quantification method described above. The results are shown in Table 2.
<Porous body having mesopores: mesoporous silica particles>
“Meso Pure” manufactured by Nippon Kasei Co., Ltd. used in Example 1 was classified to obtain a porous body having the following particle size distribution and average particle size.
Particle size distribution:> 425 μm
Average particle diameter: 566 μm
Shape: Crushed pore size: 4 nm
Pore volume: 0.7 ml / g
Specific surface area: 730 m 2 / g
[実施例7]
 以下に示す通水性層を用いた以外は、実施例1と同様に成型体サンプル7を作製し、分析サンプル7を得た。この分析サンプル7を上述のペプチド定量方法によって定量した。結果を表2に示す。
<通水性層>
日本バイリーン株式会社製不織布「FV-4365」
構成繊維:ポリエステル繊維
[Example 7]
A molded body sample 7 was produced in the same manner as in Example 1 except that the water-permeable layer shown below was used, and an analytical sample 7 was obtained. This analytical sample 7 was quantified by the peptide quantification method described above. The results are shown in Table 2.
<Water-permeable layer>
Non-woven fabric “FV-4365” manufactured by Japan Vilene Co., Ltd.
Constituent fiber: Polyester fiber
[実施例8]
 以下に示す通水性層を用いた以外は、実施例1と同様に成型体サンプル8を作製し、分析サンプル8を得た。この分析サンプル8を上述のペプチド定量方法によって定量した。結果を表2に示す。
<通水性層>
旭化成株式会社製不織布「ELTRS-N」
構成繊維:ナイロン繊維
[Example 8]
Except using the water-permeable layer shown below, the molded object sample 8 was produced similarly to Example 1, and the analysis sample 8 was obtained. This analytical sample 8 was quantified by the peptide quantification method described above. The results are shown in Table 2.
<Water-permeable layer>
Nonwoven fabric "ELTRS-N" manufactured by Asahi Kasei Corporation
Constituent fiber: Nylon fiber
[実施例9]
 以下に示す通水性層を用いた以外は、実施例1と同様に成型体サンプル9を作製し、分析サンプル9を得た。この分析サンプル9を上述のペプチド定量方法によって定量した。結果を表2に示す。
<通水性層>
旭化成株式会社製不織布「ELTRS-P」
構成繊維:ポリプロピレン繊維
[Example 9]
Except using the water-permeable layer shown below, the molded object sample 9 was produced similarly to Example 1, and the analysis sample 9 was obtained. This analytical sample 9 was quantified by the peptide quantification method described above. The results are shown in Table 2.
<Water-permeable layer>
Nonwoven fabric "ELTRS-P" manufactured by Asahi Kasei Corporation
Constituent fiber: Polypropylene fiber
[実施例10]
 以下に示すバインダを用いた以外は、実施例1と同様に成型体サンプル10を作製し、分析サンプル10を得た。この分析サンプル10を上述のペプチド定量方法によって定量した。結果を表2に示す。
<バインダ:熱可塑性樹脂粒子>
ポリエチレン(東京インキ株式会社製 PR1050SP)
MFR:24g/10min
融点:105℃
[Example 10]
A molded body sample 10 was produced in the same manner as in Example 1 except that the binder shown below was used, and an analytical sample 10 was obtained. This analytical sample 10 was quantified by the peptide quantification method described above. The results are shown in Table 2.
<Binder: Thermoplastic resin particles>
Polyethylene (PR1050SP, manufactured by Tokyo Ink Co., Ltd.)
MFR: 24g / 10min
Melting point: 105 ° C
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
 実施例4と5との対比により、通水性層の量が増加するとペプチド検出量が減少することがわかる。従って、吸・脱着材として、ペプチドの吸・脱着の観点からは通水性層は薄い方が好ましいと考えられる。実施例8~10より、通水性層の材質はPP(ポリプロピレン)よりもPET(ポリエチレンテレフタレート)が好ましく、Nylon(ナイロン)よりもPPの方が好ましいことがわかる。通水性層の材質がペプチドの検出量に及ぼす影響の詳細は不明であるが、ペプチドがメソ孔を有する多孔体に吸・脱着するだけでなく通水性層にも吸着し、その脱着のしやすさに差がある可能性が考えられる。実施例10よりペプチド検出量の点ではバインダとしてポリエチレンよりもEVAの方が好ましいことが示された。 From the comparison with Examples 4 and 5, it can be seen that the amount of detected peptide decreases as the amount of the water-permeable layer increases. Therefore, it is considered that a thin water-permeable layer is preferable as the absorption / desorption material from the viewpoint of peptide absorption / desorption. From Examples 8 to 10, it can be seen that the material of the water-permeable layer is preferably PET (polyethylene terephthalate) rather than PP (polypropylene), and PP is more preferred than Nylon (nylon). The details of the effect of the material of the water-permeable layer on the detected amount of peptide are unknown, but the peptide not only absorbs and desorbs to the porous body having mesopores, but also adsorbs to the water-permeable layer and is easy to desorb. There is a possibility that there is a difference. From Example 10, it was shown that EVA is preferable to polyethylene as a binder in terms of the amount of peptide detected.
 1,1A,1B,1C 吸・脱着材
 2 メソ孔を有する多孔体
 3 バインダ
 4 吸・脱着層
 5 不織布
 6 血液
 10 採血用スピッツ 
 21 マスク
 22,24 通水性層
 23 メソポーラスシリカ粒子層
 25 積層体
 26 吸・脱着材
1, 1A, 1B, 1C Absorption / desorption material 2 Porous body having mesopores 3 Binder 4 Absorption / desorption layer 5 Non-woven fabric 6 Blood 10 Spitz for blood collection
21 Mask 22, 24 Water-permeable layer 23 Mesoporous silica particle layer 25 Laminate 26 Absorption / desorption material

Claims (20)

  1.  生体物質を含有する液から、生体物質を選択的に吸・脱着して分離するための生体物質の選択的吸・脱着材であって、
     該吸・脱着材が、メソ孔を有する多孔体を含むシートであることを特徴とする生体物質の選択的吸・脱着材。
    A biological material selective absorption / desorption material for selectively absorbing / desorbing biological material from a liquid containing biological material,
    The selective adsorption / desorption material for biological materials, wherein the adsorption / desorption material is a sheet containing a porous body having mesopores.
  2.  前記吸・脱着材が、メソ孔を有する多孔体を含む吸・脱着層と通水性層とが積層された積層体であることを特徴とする、請求項1に記載の生体物質の選択的吸・脱着材。 2. The selective absorption of biological material according to claim 1, wherein the absorption / desorption material is a laminate in which an absorption / desorption layer including a porous body having mesopores and a water-permeable layer are laminated.・ Desorption material.
  3.  前記吸・脱着材が、メソ孔を有する多孔体を含む吸・脱着層の両面に通水性層が積層された積層体であることを特徴とする、請求項2に記載の生体物質の選択的吸・脱着材。 3. The biological material selective according to claim 2, wherein the absorbent / desorbing material is a laminate in which a water-permeable layer is laminated on both sides of an absorbent / desorbing layer including a porous body having mesopores. Absorption / desorption material.
  4.  前記吸・脱着材が、メソ孔を有する多孔体とバインダを含む層を有することを特徴とする、請求項2に記載の生体物質の選択的吸・脱着材。 The selective adsorption / desorption material for biological materials according to claim 2, wherein the adsorption / desorption material has a porous body having mesopores and a layer containing a binder.
  5.  生体物質を含有する液から、生体物質を選択的に吸・脱着して分離するための生体物質の選択的吸・脱着材であって、
     該吸・脱着材が、メソ孔を有する多孔体を含む吸・脱着層と通水性層とが積層された積層体であることを特徴とする生体物質の選択的吸・脱着材。
    A biological material selective absorption / desorption material for selectively absorbing / desorbing biological material from a liquid containing biological material,
    A selective absorption / desorption material for a biological material, wherein the absorption / desorption material is a laminate in which an absorption / desorption layer including a porous body having mesopores and a water-permeable layer are laminated.
  6.  生体物質を含有する液から、生体物質を選択的に吸・脱着して分離するための生体物質の選択的吸・脱着材であって、
     該吸・脱着材が、メソ孔を有する多孔体とバインダとを含む層を有することを特徴とする生体物質の選択的吸・脱着材。
    A biological material selective absorption / desorption material for selectively absorbing / desorbing biological material from a liquid containing biological material,
    The selective adsorption / desorption material for biological materials, wherein the adsorption / desorption material has a layer containing a porous body having mesopores and a binder.
  7.  前記メソ孔を有する多孔体のメソ孔径が2nm以上20nm以下である、請求項1~6のいずれか1項に記載の生体物質の選択的吸・脱着材。 The selective absorption / desorption material for a biological substance according to any one of claims 1 to 6, wherein the mesopore diameter of the porous body having mesopores is 2 nm or more and 20 nm or less.
  8.  前記メソ孔を有する多孔体は、平均粒子径が50μm以上700μm以下である、請求項1~7のいずれか1項に記載の生体物質の選択的吸・脱着材。 The selective absorption / desorption material for biological substances according to any one of claims 1 to 7, wherein the porous body having mesopores has an average particle diameter of 50 µm or more and 700 µm or less.
  9.  前記メソ孔を有する多孔体は、比表面積が100m/g以上1200m/g以下である、請求項1~8のいずれか1項に記載の生体物質の選択的吸・脱着材。 The selective absorption / desorption material for biological materials according to any one of claims 1 to 8, wherein the porous body having mesopores has a specific surface area of 100 m 2 / g or more and 1200 m 2 / g or less.
  10.  前記メソ孔を有する多孔体は、メソポーラスシリカ、シリカゲル、およびイオン交換樹脂からなる群から選択される1種以上を含む、請求項1~9のいずれか1項に記載の生体物質の選択的吸・脱着材。 The selective absorption of a biological substance according to any one of claims 1 to 9, wherein the porous body having mesopores includes one or more selected from the group consisting of mesoporous silica, silica gel, and ion exchange resin.・ Desorption material.
  11.  前記通水性層は、織布又は不織布である、請求項2~5及び7~10のいずれか1項に記載の生体物質の選択的吸・脱着材。 The selective absorption / desorption material for a biological material according to any one of claims 2 to 5 and 7 to 10, wherein the water-permeable layer is a woven fabric or a nonwoven fabric.
  12.  前記通水性層は、外表面に親水化処理が施されている、請求項2~11のいずれか1項に記載の生体物質の選択的吸・脱着材。 The selective absorption / desorption material for a biological material according to any one of claims 2 to 11, wherein the water-permeable layer is subjected to a hydrophilic treatment on an outer surface.
  13.  前記通水性層は、外表面に疎水化処理が施されている、請求項2~12のいずれか1項に記載の生体物質の選択的吸・脱着材。 The selective absorption / desorption material for a biological material according to any one of claims 2 to 12, wherein the water-permeable layer is subjected to a hydrophobic treatment on an outer surface.
  14.  前記生体物質がペプチドである、請求項1~13のいずれか1項に記載の生体物質の選択的吸・脱着材。 The selective adsorption / desorption material for biological material according to any one of claims 1 to 13, wherein the biological material is a peptide.
  15.  前記バインダがエチレン酢酸ビニル共重合体である、請求項4及び6~14のいずれか1項に記載の生体物質の選択的吸・脱着材。 The selective adsorption / desorption material for a biological substance according to any one of claims 4 and 6 to 14, wherein the binder is an ethylene vinyl acetate copolymer.
  16.  前記バインダは、メソ孔を有する多孔体とバインダとを含む層中に20重量%以上80重量%以下含有される、請求項4及び6~15のいずれか1項に記載の生体物質の選択的吸・脱着材。 The biological substance selective according to any one of claims 4 and 6 to 15, wherein the binder is contained in a layer containing a porous body having mesopores and a binder in an amount of 20 wt% to 80 wt%. Absorption / desorption material.
  17. 前記生体物質を含有する液を保持しうる容器であって、請求項1~16のいずれか1項に記載の吸・脱着材を内部に有する容器。 A container capable of holding a liquid containing the biological substance, the container having the absorption / desorption material according to any one of claims 1 to 16 therein.
  18.  請求項1~16のいずれか1項に記載の吸・脱着材と前記生体物質を含有する液を保持しうる容器とを含む生体物質の精製キット。 A biological material purification kit comprising the absorption / desorption material according to any one of claims 1 to 16 and a container capable of holding a liquid containing the biological material.
  19.  請求項1~16のいずれか1項に記載の生体物質の選択的吸・脱着材を、生体物質を含有する液に接触させる工程を含む、生体物質の製造方法。 A method for producing a biological material, comprising the step of bringing the selective absorbing / desorbing material for a biological material according to any one of claims 1 to 16 into contact with a liquid containing the biological material.
  20.  請求項1~16のいずれか1項に記載の生体物質の選択的吸・脱着材を、生体物質を含有する液に接触させる工程を含む、生体物質の分離方法。 A method for separating a biological material, comprising the step of bringing the selective adsorption / desorption material for biological material according to any one of claims 1 to 16 into contact with a liquid containing the biological material.
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018001057A (en) * 2016-06-28 2018-01-11 大阪ガスケミカル株式会社 Adsorbent for protein purification
WO2018092804A1 (en) 2016-11-16 2018-05-24 日本化成株式会社 Silica powder for quantitative supply, purification kit for biological material using same, and method for producing same
WO2019013228A1 (en) 2017-07-11 2019-01-17 三菱ケミカル株式会社 Silica powder storage package, and test kit using this
JP2019011132A (en) * 2017-06-30 2019-01-24 三菱ケミカル株式会社 Adsorbent storing container package adsorbing biological material

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005351800A (en) * 2004-06-11 2005-12-22 Canon Inc Biosubstance concentration method, biological substance concentration element and biosensor using biological substance concentration element
JP2009125679A (en) * 2007-11-26 2009-06-11 Panasonic Corp Gas removal filter and gas removal filter unit
WO2011062270A1 (en) * 2009-11-20 2011-05-26 シスメックス株式会社 Method for protecting analyte peptide and method for collecting analyte peptide
JP2012211043A (en) * 2011-03-31 2012-11-01 Sony Corp Porous carbon material, adsorbent, orally administrable adsorbent, adsorbent for medical use, filler for blood purification column, adsorbent for water purification, cleansing agent, carrier, agent for extended release of drugs, cell culture scaffold, mask, carbon/polymer composite, adsorbing sheet, and functional food
JP2013237266A (en) * 2012-04-16 2013-11-28 Tokushu Tokai Seishi Co Ltd Adsorption sheet for water system

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4618533A (en) * 1984-11-30 1986-10-21 Millipore Corporation Porous membrane having hydrophilic surface and process
JPH1076004A (en) * 1996-09-05 1998-03-24 Kanegafuchi Chem Ind Co Ltd Adsorbing material for humor treatment and adsorber for humor treatment
JP5196773B2 (en) * 2006-12-04 2013-05-15 キヤノン株式会社 Protein immobilization carrier
AT507847B1 (en) * 2009-01-22 2011-12-15 Fresenius Medical Care De Gmbh SORPTION AGENTS FOR REMOVING PROTEIN-BASED SUBSTANCES

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005351800A (en) * 2004-06-11 2005-12-22 Canon Inc Biosubstance concentration method, biological substance concentration element and biosensor using biological substance concentration element
JP2009125679A (en) * 2007-11-26 2009-06-11 Panasonic Corp Gas removal filter and gas removal filter unit
WO2011062270A1 (en) * 2009-11-20 2011-05-26 シスメックス株式会社 Method for protecting analyte peptide and method for collecting analyte peptide
JP2012211043A (en) * 2011-03-31 2012-11-01 Sony Corp Porous carbon material, adsorbent, orally administrable adsorbent, adsorbent for medical use, filler for blood purification column, adsorbent for water purification, cleansing agent, carrier, agent for extended release of drugs, cell culture scaffold, mask, carbon/polymer composite, adsorbing sheet, and functional food
JP2013237266A (en) * 2012-04-16 2013-11-28 Tokushu Tokai Seishi Co Ltd Adsorption sheet for water system

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018001057A (en) * 2016-06-28 2018-01-11 大阪ガスケミカル株式会社 Adsorbent for protein purification
WO2018092804A1 (en) 2016-11-16 2018-05-24 日本化成株式会社 Silica powder for quantitative supply, purification kit for biological material using same, and method for producing same
CN110023239A (en) * 2016-11-16 2019-07-16 三菱化学株式会社 The purification kit and its manufacturing method of weight feed silicon-dioxide powdery and the biological substance using the powder
JPWO2018092804A1 (en) * 2016-11-16 2019-10-17 三菱ケミカル株式会社 Silica powder for quantitative supply, biological material purification kit using the same, and method for producing the same
EP3543212A4 (en) * 2016-11-16 2019-12-04 Mitsubishi Chemical Corporation Silica powder for quantitative supply, purification kit for biological material using same, and method for producing same
JP2019011132A (en) * 2017-06-30 2019-01-24 三菱ケミカル株式会社 Adsorbent storing container package adsorbing biological material
WO2019013228A1 (en) 2017-07-11 2019-01-17 三菱ケミカル株式会社 Silica powder storage package, and test kit using this

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