WO2016017811A1 - Matériau d'adsorption/de désorption sélective de biomatériau - Google Patents

Matériau d'adsorption/de désorption sélective de biomatériau 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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desorption
absorption
mesopores
biological
porous body
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PCT/JP2015/071853
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English (en)
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/ja
Publication of WO2016017811A1 publication Critical patent/WO2016017811A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
    • B01J20/10—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing 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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  • Sampling And Sample Adjustment (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)

Abstract

La présente invention traite le problème consistant à fournir un matériau d'adsorption/de désorption sélective de biomatériau pour isoler une cible de récupération de biomatériau d'un fluide corporel ou analogue par l'intermédiaire d'une adsorption/désorption sélective ; en particulier, un matériau d'adsorption/de désorption sélective de biomatériau qui est facile à manipuler, facilite l'automatisation à l'aide d'un dispositif d'analyse, et permet d'isoler et de récupérer une cible de récupération de biomatériau rapidement, efficacement et avec un taux élevé de récupération. Ledit problème est résolu par un matériau d'adsorption/de désorption sélective de biomatériau pour isoler une cible de récupération de biomatériau d'un liquide contenant un biomatériau par l'intermédiaire d'une absorption/désorption sélective, ledit matériau d'adsorption/de désorption sélective de biomatériau étant caractérisé en ce qu'il est une feuille qui contient un corps poreux qui présente des mésopores.
PCT/JP2015/071853 2014-08-01 2015-07-31 Matériau d'adsorption/de désorption sélective de biomatériau WO2016017811A1 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018001057A (ja) * 2016-06-28 2018-01-11 大阪ガスケミカル株式会社 タンパク質精製用吸着剤
WO2018092804A1 (fr) 2016-11-16 2018-05-24 日本化成株式会社 Poudre de silice pour alimentation quantitative, kit de purification pour matériau biologique l'utilisant, et sa méthode de production
WO2019013228A1 (fr) 2017-07-11 2019-01-17 三菱ケミカル株式会社 Emballage de stockage de poudre de silice et trousse de test l'utilisant
JP2019011132A (ja) * 2017-06-30 2019-01-24 三菱ケミカル株式会社 生体物質を吸着させる吸着材収納容器パッケージ

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005351800A (ja) * 2004-06-11 2005-12-22 Canon Inc 生体物質濃縮方法、生体物質濃縮素子、及び、生体物質濃縮素子を用いたバイオセンサ
JP2009125679A (ja) * 2007-11-26 2009-06-11 Panasonic Corp ガス除去フィルタおよびガス除去フィルタユニット
WO2011062270A1 (fr) * 2009-11-20 2011-05-26 シスメックス株式会社 Procédé de protection d'un peptide analyte et procédé de recueil d'un peptide analyte
JP2012211043A (ja) * 2011-03-31 2012-11-01 Sony Corp 多孔質炭素材料、吸着剤、経口投与吸着剤、医療用吸着剤、血液浄化カラム用の充填剤、水浄化用吸着剤、クレンジング剤、担持体、薬剤徐放剤、細胞培養足場材、マスク、炭素／ポリマー複合体、吸着シート、及び、機能性食品
JP2013237266A (ja) * 2012-04-16 2013-11-28 Tokushu Tokai Seishi Co Ltd 水系用吸着シート

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 (ja) * 1996-09-05 1998-03-24 Kanegafuchi Chem Ind Co Ltd 体液処理用吸着材及び体液処理用吸着器
JP5196773B2 (ja) * 2006-12-04 2013-05-15 キヤノン株式会社 タンパク質固定化担体
AT507847B1 (de) * 2009-01-22 2011-12-15 Fresenius Medical Care De Gmbh Sorptionsmittel zum entfernen proteingebundener substanzen

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005351800A (ja) * 2004-06-11 2005-12-22 Canon Inc 生体物質濃縮方法、生体物質濃縮素子、及び、生体物質濃縮素子を用いたバイオセンサ
JP2009125679A (ja) * 2007-11-26 2009-06-11 Panasonic Corp ガス除去フィルタおよびガス除去フィルタユニット
WO2011062270A1 (fr) * 2009-11-20 2011-05-26 シスメックス株式会社 Procédé de protection d'un peptide analyte et procédé de recueil d'un peptide analyte
JP2012211043A (ja) * 2011-03-31 2012-11-01 Sony Corp 多孔質炭素材料、吸着剤、経口投与吸着剤、医療用吸着剤、血液浄化カラム用の充填剤、水浄化用吸着剤、クレンジング剤、担持体、薬剤徐放剤、細胞培養足場材、マスク、炭素／ポリマー複合体、吸着シート、及び、機能性食品
JP2013237266A (ja) * 2012-04-16 2013-11-28 Tokushu Tokai Seishi Co Ltd 水系用吸着シート

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018001057A (ja) * 2016-06-28 2018-01-11 大阪ガスケミカル株式会社 タンパク質精製用吸着剤
WO2018092804A1 (fr) 2016-11-16 2018-05-24 日本化成株式会社 Poudre de silice pour alimentation quantitative, kit de purification pour matériau biologique l'utilisant, et sa méthode de production
CN110023239A (zh) * 2016-11-16 2019-07-16 三菱化学株式会社 定量供给用二氧化硅粉体、以及使用该粉体的生物物质的纯化试剂盒及其制造方法
JPWO2018092804A1 (ja) * 2016-11-16 2019-10-17 三菱ケミカル株式会社 定量供給用シリカ粉体、並びにこれを用いた生体物質の精製キット及びその製造方法
EP3543212A4 (fr) * 2016-11-16 2019-12-04 Mitsubishi Chemical Corporation Poudre de silice pour alimentation quantitative, kit de purification pour matériau biologique l'utilisant, et sa méthode de production
JP2019011132A (ja) * 2017-06-30 2019-01-24 三菱ケミカル株式会社 生体物質を吸着させる吸着材収納容器パッケージ
WO2019013228A1 (fr) 2017-07-11 2019-01-17 三菱ケミカル株式会社 Emballage de stockage de poudre de silice et trousse de test l'utilisant

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