JP2010214245A - Porous membrane with fixed graft chain having functional group, manufacturing method therefor and application - Google Patents
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Landscapes
- Manufacture Of Macromolecular Shaped Articles (AREA)
- Graft Or Block Polymers (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
Description
本発明は、目的物と相互作用する官能基を有するグラフト鎖が、多孔膜の細孔内部に固定された多孔膜、その製造方法およびそのような多孔膜を用いた目的物の分離方法に関する。 The present invention relates to a porous membrane in which a graft chain having a functional group that interacts with a target product is fixed inside the pores of the porous membrane, a method for producing the same, and a method for separating a target product using such a porous membrane.
膜を用いて目的物を分離する分野において、分離対象物および分離メカニズム等の違いに応じ、極めて多様な分離膜が存在する。現在工業的に利用されている分離膜は、その分離メカニズムにより大別すると、（１）分離対象物のサイズを利用してろ過する分離膜（例えば、精密ろ過膜（ＭＦ）、限外ろ過膜（ＵＦ）、ナノフィルトレーション膜（ＮＦ）等）、（２）分離対象物と膜素材との分子レベルでの相互作用および拡散を利用する分離膜（例えば、電解膜（ＭＥ）、透析膜（ＤＤ）、膜蒸留（ＭＤ）、浸透気化膜（ＰＶ）等）、の２群に分けられる。また、分離膜の形態により大別すると、多孔質や均質な素材よりなる対称膜および膜の厚みや方向によって孔径分布や材質等が異なる非対称膜に分けられる。 In the field of separating an object using a membrane, there are a great variety of separation membranes depending on the difference in separation object, separation mechanism, and the like. Separation membranes currently used industrially can be broadly classified according to their separation mechanisms. (1) Separation membranes that filter using the size of the object to be separated (for example, microfiltration membranes (MF), ultrafiltration membranes) (UF), nanofiltration membrane (NF), etc.), (2) Separation membrane (for example, electrolytic membrane (ME), dialysis membrane) that utilizes interaction and diffusion at the molecular level between the separation object and the membrane material (DD), membrane distillation (MD), pervaporation membrane (PV), etc.). Further, when roughly classified according to the form of the separation membrane, it can be divided into a symmetric membrane made of a porous or homogeneous material, and an asymmetric membrane having different pore diameter distribution and material depending on the thickness and direction of the membrane.
一方、目的物の分離技術として、膜を用いた方法以外に吸着による方法も広く工業的に用いられている。例えば、選択的な吸着性を有する樹脂をパッキングしたカラムクロマトグラフィーによるタンパク質の分離精製、モレキュラーシーブによる高度に脱水された有機溶剤の精製、活性炭による有機粒状物質の吸着除去による水処理などは、それぞれの分野において重要な分離技術として活用されている。 On the other hand, as a technique for separating a target product, an adsorption method is widely used industrially in addition to a method using a membrane. For example, separation and purification of proteins by column chromatography packed with selective adsorptive resin, purification of highly dehydrated organic solvent by molecular sieve, water treatment by adsorption removal of organic particulate matter by activated carbon, etc. It is used as an important separation technology in the field of
膜技術と吸着技術の両方の要素を併せ持つ技術、即ち、特定の物質、分子またはイオン等を特異的に吸着する膜は、吸着膜またはアフィニティ膜と呼ばれ、これについても多くの報告がなされている。とくにイオン吸着膜は純水中の金属イオンなどを吸着除去し、超純水を得る方法として水処理の分野で広く工業的に使われている。 A technology that combines elements of both membrane technology and adsorption technology, that is, a membrane that specifically adsorbs a specific substance, molecule or ion is called an adsorption membrane or an affinity membrane, and many reports have been made about this. Yes. In particular, ion adsorption membranes are widely used industrially in the field of water treatment as a method of obtaining ultrapure water by adsorbing and removing metal ions and the like in pure water.
イオンよりサイズの大きな分子、特にタンパク質を対象とした吸着膜技術も多く報告されている。例えば特許文献１には多孔質基材の細孔表面に負電荷を持つ官能基を固定することにより、水溶液中で正電荷に帯電したリゾチームなどのタンパク質分子を選択的に吸着し、目的とするタンパク質を精製する吸着膜とその分離方法が記載されている。また特許文献２には多孔質基材の細孔表面に正電荷を持つ官能基を固定することにより、水溶液中で負電荷に帯電したエンドトキシンなどのタンパク質分子を選択的に吸着し、目的とするタンパク質を精製する吸着膜とその分離方法が記載されている。 There have been many reports of adsorption membrane technology for molecules larger than ions, especially proteins. For example, in Patent Document 1, a functional group having a negative charge is immobilized on the pore surface of a porous substrate, thereby selectively adsorbing protein molecules such as lysozyme charged to a positive charge in an aqueous solution. An adsorption membrane for purifying proteins and a method for separating the same are described. Patent Document 2 discloses a method of selectively adsorbing protein molecules such as endotoxin charged negatively in an aqueous solution by immobilizing a functional group having a positive charge on the pore surface of a porous substrate. An adsorption membrane for purifying proteins and a method for separating the same are described.
非特許文献１〜３は、多孔膜へのタンパク質の吸着量を増やすために、官能基をグラフト鎖に固定し、このグラフト鎖を多孔質基材に固定した多孔膜について報告している。これらの多孔膜では、１本のグラフト鎖に多数の官能基が固定されているため、タンパク質が多孔膜の表面だけでなく細孔内でも立体的に吸着し、吸着量は表面だけの吸着に比べて大きく増加する。 Non-Patent Documents 1 to 3 report a porous membrane in which a functional group is fixed to a graft chain and the graft chain is fixed to a porous substrate in order to increase the amount of protein adsorbed to the porous membrane. In these porous membranes, since a large number of functional groups are fixed to one graft chain, proteins adsorb three-dimensionally not only on the surface of the porous membrane but also in the pores, and the amount of adsorption is limited to the adsorption of only the surface. Compared to a large increase.
上記のように、膜技術と吸着技術を兼ね備えた吸着膜技術については多くの報告がされている。しかしながら、こうした技術が工業的に活用されている例は、例えば医薬品精製プロセスでのカラムクロマトグフィーによる吸着技術の利用に比べると非常に少ないのが現状である。この理由の一つとして、カラムクロマトグラフィーでは、拡散によって細孔内に目的物（タンパク質等）が移動し、接触した官能基に吸着するという拡散の原理に基づいているため、用いる樹脂の比表面積は非常に大きく、それに応じて目的物の吸着量が顕著に多くなるのに対し、吸着膜では対流の原理に基づいて目的物の吸着がなされるため、膜の比表面積はカラムクロマトグラフィーの樹脂に比べて小さく、目的物の吸着量も少ないことが挙げられる。 As described above, many reports have been made on the adsorption membrane technology that combines the membrane technology and the adsorption technology. However, there are very few examples in which such a technique is industrially used compared to the use of an adsorption technique by column chromatography in a pharmaceutical purification process, for example. One reason for this is that, in column chromatography, the specific surface area of the resin used is based on the principle of diffusion, in which the target substance (protein, etc.) moves into the pores by diffusion and is adsorbed to the functional group in contact. Is very large, and the amount of adsorption of the target is significantly increased accordingly, whereas the adsorption membrane absorbs the target based on the principle of convection, so the specific surface area of the membrane is the resin for column chromatography. The amount of adsorption of the target product is small.
実際、特許文献１および２に報告されたタンパク質吸着膜は、タンパク質を含む水溶液を高流速で通液しても、タンパク質の吸着がなされることから迅速な処理には有効であるが、タンパク質の吸着が膜の表面のみで行われるため、その吸着量は比表面積に依存し、多孔質のビーズを用いたカラムクロマトグラフィーに比べて吸着量は著しく低い。 In fact, the protein adsorption membranes reported in Patent Documents 1 and 2 are effective for rapid treatment because protein adsorption is performed even when an aqueous solution containing protein is passed at a high flow rate. Since the adsorption is performed only on the surface of the membrane, the amount of adsorption depends on the specific surface area, and the amount of adsorption is significantly lower than that of column chromatography using porous beads.
非特許文献１〜３に報告されたタンパク質吸着膜は、表面のみに吸着する膜に比べればタンパク質の吸着量は多いものの、特に低流速においてはカラムクロマトグラフィーの樹脂の吸着量には及ばない。また、塩を含む溶液を通液することは、吸着したタンパク質を溶出するために不可欠な工程であるが、非特許文献１〜３に報告された多孔膜は、塩を含む溶液を通液した際に５％〜１０％も伸張変形するという実用上重大な問題が生じる。 Although the protein adsorption membranes reported in Non-Patent Documents 1 to 3 have a larger amount of protein adsorption than membranes adsorbed only on the surface, they do not reach the column chromatography resin adsorption amount, particularly at low flow rates. In addition, passing a solution containing a salt is an indispensable step for eluting the adsorbed protein, but the porous membranes reported in Non-Patent Documents 1 to 3 have passed a solution containing a salt. In this case, there is a serious problem in practice that the film is stretched and deformed by 5% to 10%.
吸着量の少なさは、高流速で迅速に処理できるという利点で補われると考えられる。しかしながら、タンパク質精製プロセスでは、タンパク質の吸着が進み、破過が開始され、タンパク質が漏出する直前またはそれと同時に通液を停止することが、透過液中から除去することが求められるタンパク質の漏出の制御に必要とされ、高流速での処理の場合、その停止時の判断が容易でない。そのため、実際の工業的な利用では、吸着膜によるタンパク質精製プロセスはカラムクロマトグラフィーによるプロセス以上に、厳密なバリデーションが要求される。このことが、タンパク質精製プロセスでの吸着膜の工業的な利用を妨げる重大な理由となっている。既存のタンパク吸着膜には、デプスろ過膜のように、捕捉した対象物の透過側への漏出を防止する機能が備わっておらず、例えば、特許文献１および２の吸着膜では、官能基が多孔膜の表面にのみ固定されているため、表面の全てにタンパク質等が吸着すると、非吸着のタンパク質等が透過側に漏出する。また、非特許文献１〜３のグラフト鎖を有する吸着膜の場合、グラフト鎖の多孔膜への導入量を多くすると、導入されるグラフト鎖の多くが多孔膜の基材内部に固定されるというその製法の原理上、多孔膜の基材自体が膨張することが避けられず、その結果細孔径が拡大し、グラフト鎖を細孔空間内全体に充填することができず、デプスろ過膜としての機能を付与することができない。 It is considered that the small amount of adsorption is compensated by the advantage that it can be processed quickly at a high flow rate. However, in the protein purification process, protein adsorption proceeds, breakthrough is initiated, and stopping the flow just before or simultaneously with protein leakage controls the protein leakage that is required to be removed from the permeate. In the case of processing at a high flow rate, it is not easy to judge at the time of stopping. Therefore, in actual industrial use, the protein purification process using an adsorption membrane requires stricter validation than the process using column chromatography. This is an important reason for hindering the industrial use of adsorption membranes in protein purification processes. The existing protein adsorption membrane does not have a function to prevent leakage of the captured object to the permeation side unlike the depth filtration membrane. For example, in the adsorption membranes of Patent Documents 1 and 2, the functional group has no functional group. Since it is fixed only on the surface of the porous membrane, when protein or the like is adsorbed on the entire surface, non-adsorbed protein or the like leaks to the permeate side. Moreover, in the case of the adsorption film | membrane which has the graft chain of a nonpatent literature 1-3, when the introduction amount to the porous membrane of a graft chain is increased, many graft chains introduced will be fixed inside the base material of a porous membrane. Due to the principle of the manufacturing method, it is inevitable that the porous membrane base material itself expands. As a result, the pore diameter is enlarged, and the graft chain cannot be filled in the entire pore space. A function cannot be added.
かかる状況に鑑み、本発明の解決しようとする課題は、タンパク質等の目的物を含有する溶液からの、高流速での迅速な目的物の分離が可能な多孔膜であって、破過後の目的物の漏出が抑制され、塩溶液等の通液による伸長変形が抑制された、形状安定性の高い、新規多孔膜を提供することである。また、かかる吸着多孔膜を用いた、タンパク質等の粒子状の目的物の分離方法、さらには水と有機溶媒の混合物等の分離方法を提供することである。 In view of such a situation, the problem to be solved by the present invention is a porous membrane capable of quickly separating a target object at a high flow rate from a solution containing the target object such as protein, and the purpose after breakthrough It is an object of the present invention to provide a novel porous membrane with high shape stability, in which leakage of substances is suppressed and elongation deformation due to passage of salt solution or the like is suppressed. Another object of the present invention is to provide a method for separating a particulate object such as a protein and a method for separating a mixture of water and an organic solvent using such an adsorption porous membrane.
本発明者らは、上記の課題を解決するために鋭意検討した結果、官能基を有するグラフト鎖が固定された多孔膜であって、全グラフト鎖の所定量以上が細孔空間内を含む多孔膜表面に固定された多孔膜を製造する方法を見出し、該多孔膜を用いることにより、タンパク質等の粒子状の目的物を、破過後も透過液への漏出なく捕捉できることを見出した。また、該多孔膜を用いることにより、水と有機溶媒の混合液を膜蒸留で分離できることを見出し、本発明を完成した。 As a result of intensive studies to solve the above problems, the inventors of the present invention are porous membranes in which a graft chain having a functional group is fixed, and a predetermined amount or more of all graft chains are included in the pore space. A method for producing a porous membrane fixed on the membrane surface has been found, and by using the porous membrane, it has been found that particulate objects such as proteins can be captured without leaking into the permeate even after breakthrough. Moreover, it discovered that the liquid mixture of water and an organic solvent was separable by membrane distillation by using this porous membrane, and completed this invention.
すなわち、本発明は、官能基を有するグラフト鎖が固定された多孔膜であって、前記グラフト鎖の少なくとも３０％以上が、前記多孔膜の表面に固定されている、多孔膜に関する。
本発明はまた、前記グラフト鎖の少なくとも５０％〜９９％が、前記多孔膜の表面に固定されている、前記の多孔膜に関する。
本発明はまた、前記官能基が、アニオン交換基、カチオン交換基および疎水性基からなる群より選択される、前記の多孔膜に関する。
本発明はまた、前記グラフト鎖の多孔膜へのグラフト率が８０％〜３００％である、前記の多孔膜に関する。
本発明はまた、前記グラフト鎖がグリシジルメタクリレートの重合体を含む、前記の多孔膜に関する。
さらに、本発明は、最大細孔径０．１μｍ〜１．０μｍ、空孔率５０％〜９５％の多孔膜に、−１０℃〜２０℃でグラフト鎖の重合反応を行うことにより、グラフト鎖を導入する工程；およびグラフト鎖に官能基を導入する工程；を含む、官能基を有するグラフト鎖が固定された多孔膜の製造方法に関する。
さらに、本発明は、アニオン交換基、カチオン交換基および疎水性基からなる群より選択される官能基を有するグラフト鎖が固定された多孔膜であって、前記グラフト鎖の少なくとも３０％以上が前記多孔膜の表面に固定されている多孔膜に、分離目的物含有溶液を通液する工程を含む、目的物の分離方法に関する。
さらに、本発明は、疎水性基を有するグラフト鎖が固定された多孔膜であって、前記グラフト鎖の少なくとも３０％以上が前記多孔膜の表面に固定されている多孔膜を介して、有機物−水混合溶液を蒸発させる工程を含む、水または有機物の分離方法に関する。
That is, the present invention relates to a porous film in which a graft chain having a functional group is fixed, and at least 30% or more of the graft chain is fixed to the surface of the porous film.
The present invention also relates to the porous membrane, wherein at least 50% to 99% of the graft chains are fixed to the surface of the porous membrane.
The present invention also relates to the porous membrane, wherein the functional group is selected from the group consisting of an anion exchange group, a cation exchange group and a hydrophobic group.
The present invention also relates to the porous membrane, wherein a graft ratio of the graft chain to the porous membrane is 80% to 300%.
The present invention also relates to the above porous membrane, wherein the graft chain contains a polymer of glycidyl methacrylate.
Furthermore, the present invention provides a graft chain polymerization reaction at −10 ° C. to 20 ° C. on a porous membrane having a maximum pore size of 0.1 μm to 1.0 μm and a porosity of 50% to 95%. And a step of introducing a functional group into the graft chain. The present invention relates to a method for producing a porous membrane to which a graft chain having a functional group is fixed.
Furthermore, the present invention is a porous membrane to which a graft chain having a functional group selected from the group consisting of an anion exchange group, a cation exchange group and a hydrophobic group is fixed, wherein at least 30% or more of the graft chain is the above-mentioned The present invention relates to a method for separating an object comprising a step of passing a solution containing an object for separation through a porous film fixed to the surface of the porous film.
Furthermore, the present invention provides a porous membrane in which a graft chain having a hydrophobic group is immobilized, wherein at least 30% or more of the graft chain is immobilized on the surface of the porous membrane via the porous membrane. The present invention relates to a method for separating water or organic matter, including a step of evaporating a water mixed solution.
本発明の多孔膜を用いることにより、目的物を含有する溶液から、迅速に、目的物の漏出を抑制して、効率よく目的物を分離することができる。 By using the porous membrane of the present invention, the target product can be efficiently separated from the solution containing the target product quickly by suppressing leakage of the target product.
以下、本発明を実施するための形態（以下、「本実施の形態」という。）について詳細に説明する。なお、本発明は、以下の本実施の形態に限定されるものではなく、その要旨の範囲内で種々変形して実施することができる。 Hereinafter, a mode for carrying out the present invention (hereinafter referred to as “the present embodiment”) will be described in detail. The present invention is not limited to the following embodiment, and can be implemented with various modifications within the scope of the gist.
本実施の形態における「官能基を有するグラフト鎖が固定された多孔膜」とは、多孔膜に、官能基を有するグラフト鎖が化学的に固定されている多孔膜を言う。 The “porous membrane in which a graft chain having a functional group is fixed” in the present embodiment refers to a porous membrane in which a graft chain having a functional group is chemically fixed to the porous membrane.
本実施の形態において、多孔膜の基材は特に限定されないが、機械的性質の保持という観点から、ポリオレフィン系重合体から構成されていることが好ましい。ポリオレフィン系重合体としては、例えば、エチレン、プロピレン、ブチレンおよびフッ化ビニリデンなどのオレフィンの単独重合体、前記オレフィンの２種以上の共重合体、または１種もしくは２種以上のオレフィンとパーハロゲン化オレフィンとの共重合体などが挙げられる。これらの重合体の２種以上の混合物であってもよい。パーハロゲン化オレフィンとしては、例えばテトラフルオロエチレンおよびクロロトリフルオロエチレンなどが挙げられる。これらの中でも、機械的強度に特に優れ、かつタンパク質等の分離目的物の高い吸着容量が得られる素材であるという観点から、ポリエチレンまたはポリフッ化ビニリデンが好ましく、ポリエチレンがより好ましい。 In the present embodiment, the substrate of the porous film is not particularly limited, but is preferably composed of a polyolefin-based polymer from the viewpoint of maintaining mechanical properties. Examples of the polyolefin-based polymer include homopolymers of olefins such as ethylene, propylene, butylene and vinylidene fluoride, copolymers of two or more of the olefins, or perhalogenation with one or more of the olefins. Examples thereof include copolymers with olefins. A mixture of two or more of these polymers may be used. Examples of the perhalogenated olefin include tetrafluoroethylene and chlorotrifluoroethylene. Among these, polyethylene or polyvinylidene fluoride is preferable, and polyethylene is more preferable from the viewpoint of being excellent in mechanical strength and capable of obtaining a high adsorption capacity of a separation target product such as protein.
多孔膜の形態は、溶液の通液または気体の通過が可能な形態であれば特に限定されず、たとえば、平膜、不織布、中空糸膜、モノリス、キャピラリー、円板または円筒状などが挙げられる。これらの形態の中でも、製造のし易さ、スケールアップ性、モジュール成型した際の膜のパッキング性などの観点から、多孔膜は、中空糸多孔膜であることが好ましい。中空糸多孔膜とは、中空部分を有する円筒状または繊維状の多孔膜であり、中空糸の内層と外層が貫通孔である細孔によって連続しており、その細孔によって内層から外層あるいは外層から内層に、液体または気体が透過する性質を有する多孔体を意味する。中空糸多孔膜の外径および内径は、物理的に形状を保持することができ、かつモジュール成型可能であれば、特に限定されない。ポリオレフィン系重合体を用いて中空糸多孔膜を製造する方法は、当業者にとって公知であり、例えば、特開平３−４２０２５号公報に開示される方法などが挙げられる。 The form of the porous membrane is not particularly limited as long as the solution can be passed or the gas can pass therethrough, and examples thereof include a flat membrane, a nonwoven fabric, a hollow fiber membrane, a monolith, a capillary, a disc, and a cylindrical shape. . Among these forms, the porous membrane is preferably a hollow fiber porous membrane from the viewpoint of ease of production, scale-up property, and packing property of the membrane when it is molded into a module. The hollow fiber porous membrane is a cylindrical or fibrous porous membrane having a hollow portion, and the inner layer and the outer layer of the hollow fiber are continuous by pores that are through holes, and the inner layer to the outer layer or the outer layer by the pores. Means a porous body having a property of allowing liquid or gas to permeate into the inner layer. The outer diameter and inner diameter of the hollow fiber porous membrane are not particularly limited as long as the shape can be physically maintained and module molding is possible. A method for producing a hollow fiber porous membrane using a polyolefin polymer is known to those skilled in the art, and examples thereof include a method disclosed in JP-A-3-42025.
本実施の形態の多孔膜は、多孔膜に固定された全グラフト鎖（官能基を有するものも有さないものも含む）のうち、３０％以上が前記多孔膜の表面に固定されていることを特徴とする。多孔膜において、グラフト鎖は、その表面および内部（すなわち基材の内部）のいずれにも固定されることができるが、この多孔膜に固定された全グラフト鎖のうち３０％以上、好ましくは５０％〜９９％、より好ましくは６０％〜９５％、さらに好ましくは７０％〜９５％が、前記多孔膜の表面に固定されている。このような特徴を有する多孔膜は、分離目的物を含む溶液を通液させて目的物を分離する際、破過した時点で、デプスろ過膜のように、目的物の漏出を防止する機能を有する。また、基材の内部に固定されているグラフト鎖の比率が低いため、多孔膜に塩溶液を通液した際の膜の伸長変形が抑えられる。 In the porous membrane of the present embodiment, 30% or more of all graft chains (including those having a functional group and those having no functional group) fixed to the porous membrane are fixed to the surface of the porous membrane. It is characterized by. In the porous membrane, the graft chains can be fixed either on the surface or inside (that is, inside the substrate), but 30% or more, preferably 50% of the total graft chains fixed on the porous membrane. % To 99%, more preferably 60% to 95%, and even more preferably 70% to 95% are fixed on the surface of the porous membrane. The porous membrane having such characteristics has a function of preventing leakage of the target object like a depth filtration membrane when it breaks through when the target object is separated by passing a solution containing the target object. Have. In addition, since the ratio of the graft chain fixed inside the substrate is low, the membrane is prevented from being deformed when the salt solution is passed through the porous membrane.
本実施の形態において、「グラフト鎖」とは、上記の多孔膜の基材と同種または異種の分子鎖であり、モノマーの重合体を含む。 In the present embodiment, the “graft chain” is a molecular chain that is the same or different from the base material of the porous membrane, and includes a monomer polymer.
グラフト鎖を構成する重合体としては、例えば、グリシジルメタクリレート、酢酸ビニル、ヒドロキシプロピルアセテートまたはこれらのいずれか２種以上のモノマーの重合体が挙げられるが、アニオン交換基、カチオン交換基および疎水性基等の官能基を導入しやすいことから、グリシジルメタクリレートの重合体がより好ましい。グラフト鎖を含まない基材重量に対するグラフト鎖の重量の比として表される全体のグラフト率は、例えば後述の実施例等に記載の手法を用いて測定することができ、より高い吸着容量および力学的に安定な強度をともに確保し、また、分離目的物を含む溶液を通液させて目的物を分離する際、破過した時点で目的物の漏出を防止するという観点から、好ましくは８０％〜３００％であり、より好ましくは１００％〜２５０％であり、さらに好ましくは１２０％〜２００％である。グラフト率が８０％未満の多孔膜であっても、塩溶液等の通液による伸張変形が抑制され、形状安定性に優れた多孔膜として使用することができる。 Examples of the polymer constituting the graft chain include glycidyl methacrylate, vinyl acetate, hydroxypropyl acetate, and polymers of any two or more of these monomers. An anion exchange group, a cation exchange group, and a hydrophobic group. A polymer of glycidyl methacrylate is more preferable because it can easily introduce functional groups such as. The overall graft ratio expressed as the ratio of the weight of the graft chain to the weight of the base material not including the graft chain can be measured, for example, using the technique described in the examples and the like described later, and higher adsorption capacity and dynamics. From the viewpoint of ensuring both stable strength and separating the target product by passing a solution containing the target product, 80% is preferable from the viewpoint of preventing leakage of the target product at the time of breakthrough. It is -300%, More preferably, it is 100%-250%, More preferably, it is 120%-200%. Even a porous membrane having a graft ratio of less than 80% can be used as a porous membrane having excellent shape stability because it is prevented from stretching deformation due to the passage of a salt solution or the like.
グラフト鎖が有する官能基は特に限定されず、例えば選択的に吸着・分離しようとする目的物に応じて適宜選択することができ、実用的な使用を考慮すれば、アニオン交換基、カチオン交換基および疎水性基から選ばれることが好ましい。アニオン交換基は負に帯電した目的物を、カチオン交換基は正に帯電した目的物を、また疎水性基は疎水性の性質を有する目的物を選択的に分離するために用いることができる。 The functional group possessed by the graft chain is not particularly limited, and can be appropriately selected according to the object to be selectively adsorbed / separated. In consideration of practical use, an anion exchange group, a cation exchange group And a hydrophobic group. An anion exchange group can be used for selectively separating a negatively charged target product, a cation exchange group for a positively charged target product, and a hydrophobic group for selectively separating a target product having hydrophobic properties.
アニオン交換基としては、例えば、ジエチルアミノ基（ＤＥＡ、Ｅｔ2Ｎ−）、四級アンモニウム基（Ｑ、Ｒ3Ｎ+−）、四級アミノエチル基（ＱＡＥ、Ｒ3Ｎ+−（ＣＨ2）2−）、ジエチルアミノエチル基（ＤＥＡＥ、Ｅｔ2Ｎ−（ＣＨ2）2−）、ジエチルアミノプロピル基（ＤＥＡＰ、Ｅｔ2Ｎ−（ＣＨ2）3−）などが挙げられる。ここで、Ｒは、特に限定されず、同一のＮに結合するＲが同一または異なっていてもよく、好適には、アルキル基、フェニル基、アラルキル基などの炭化水素基を表す。四級アンモニウム基としては、例えば、トリメチルアミノ基（トリメチルアンモニウム基、Ｍｅ3Ｎ+−）などが挙げられる。グラフト鎖への導入の簡便性および吸着容量の高さという観点からは、ＤＥＡおよびＱが好ましく、ＤＥＡがより好ましい。 Examples of the anion exchange group include a diethylamino group (DEA, Et 2 N—), a quaternary ammonium group (Q, R 3 N + —), a quaternary aminoethyl group (QAE, R 3 N + — (CH 2 )). 2 -), diethylaminoethyl group (DEAE, Et 2 N- (CH 2) 2 -), diethylaminopropyl group (DEAP, Et 2 N- (CH 2) 3 -) , and the like. Here, R is not particularly limited, and R bonded to the same N may be the same or different, and preferably represents a hydrocarbon group such as an alkyl group, a phenyl group, or an aralkyl group. Examples of the quaternary ammonium group include a trimethylamino group (trimethylammonium group, Me 3 N + -). DEA and Q are preferable, and DEA is more preferable from the viewpoint of ease of introduction into the graft chain and high adsorption capacity.
カチオン交換基としては、例えば、スルホプロピル基（ＳＰ、ＳＯ3Ｈ−（ＣＨ2）3−）、スルホン基（−SO3H）、カルボキシル基（ＣＯＯＨ−）などが挙げられる。 Examples of the cation exchange group include a sulfopropyl group (SP, SO 3 H— (CH 2 ) 3 —), a sulfone group (—SO 3 H), a carboxyl group (COOH—), and the like.
疎水性基としては、例えば、フェニル基、オクチル基、ブチル基などが挙げられる。 Examples of the hydrophobic group include a phenyl group, an octyl group, and a butyl group.
以下に、本実施の形態における多孔膜の製造方法について説明する。最大細孔径０．１μｍ〜１．０μｍ、空孔率５０％〜９５％の多孔膜に、−１０℃〜２０℃でグラフト鎖の重合反応を行うことによりグラフト鎖を導入する工程；およびグラフト鎖に官能基を導入する工程；を含む方法により、本実施の形態に係る、官能基を有するグラフト鎖が固定された多孔膜を製造することができる。上記の方法において、所望の本実施の形態に係る官能基を有するグラフト鎖が固定された多孔膜が得られる限り、多孔膜グラフト鎖に官能基を導入する工程を、多孔膜にグラフト鎖を導入する工程に先立って行ってもよい。 Below, the manufacturing method of the porous film in this Embodiment is demonstrated. A step of introducing a graft chain into a porous membrane having a maximum pore diameter of 0.1 μm to 1.0 μm and a porosity of 50% to 95% by carrying out a polymerization reaction of the graft chain at −10 ° C. to 20 ° C .; By the method including the step of introducing a functional group into the porous membrane according to the present embodiment, the graft chain having the functional group is fixed. In the above method, the step of introducing the functional group into the porous membrane graft chain is introduced as long as the porous membrane having the desired graft chain having the functional group according to the present embodiment is obtained. It may be performed prior to the step of performing.
上記の本実施の形態の製造方法において、グラフト鎖を導入しようとする多孔膜の最大細孔径は、グラフト鎖が細孔空間内を含む多孔膜表面の全体に固定され、かつ官能基を有するグラフト鎖が固定された多孔膜を溶液が通液可能な範囲であることが好ましい。このような観点から、最大細孔径の範囲は、好ましくは０．０１μｍ〜３μｍであり、より好ましくは０．５μｍ〜２μｍであり、さらに好ましくは０．１μｍ〜１μｍである。 In the manufacturing method of the present embodiment described above, the maximum pore diameter of the porous membrane to which graft chains are to be introduced is a graft having a graft chain fixed to the entire porous membrane surface including the pore space and having a functional group. It is preferable that the solution can pass through the porous membrane with the chain fixed. From such a viewpoint, the range of the maximum pore diameter is preferably 0.01 μm to 3 μm, more preferably 0.5 μm to 2 μm, and further preferably 0.1 μm to 1 μm.
上記の本実施の形態の製造方法において、グラフト鎖を導入しようとする多孔膜中の細孔の占める体積である空孔率は、多孔膜の形状を保持しかつグラフト鎖が細孔空間内を含む多孔膜表面の全体に固定される範囲となるよう、好ましくは５０％〜９５％であり、より好ましくは６０％〜９０％であり、さらに好ましくは６０％〜８０％である。 In the manufacturing method of the present embodiment described above, the porosity, which is the volume occupied by the pores in the porous membrane into which the graft chain is to be introduced, maintains the shape of the porous membrane and the graft chain remains within the pore space. Preferably, it is 50% to 95%, more preferably 60% to 90%, and still more preferably 60% to 80%, so that the entire surface of the porous membrane is fixed.
上記最大細孔径および空孔率の測定は、Ｍａｒｃｅｌ Ｍｕｌｄｅｒ著「膜技術」（株式会社アイピーシー）などに記載されているような、当業者にとって公知の方法により行うことができる。例えば最大細孔径の測定は、後述の実施例等に記載のバブルポイント法による評価を適切に用いることができる。 The measurement of the maximum pore diameter and the porosity can be performed by a method known to those skilled in the art, such as described in “Membrane Technology” by Marcel Mulder (IPC Co., Ltd.). For example, the measurement by the bubble point method described in the below-mentioned Examples etc. can be used appropriately for the measurement of the maximum pore diameter.
多孔膜にグラフト鎖を導入する方法としては、多孔膜に反応点となるラジカルを発生させ、これを基点として、２重結合を有するモノマーを重合させてグラフト鎖の重合反応を行う方法が挙げられる。この際のラジカルの発生方法としては、酸素を遮断した条件下、多孔膜にγ線または電子線等の放射線を照射し、多孔膜の結晶成分内にラジカルを発生させる方法が好ましい。このときの照射線量は好ましくは１０ｋＧｙ〜５００ｋＧｙであり、より好ましくは２０ｋＧｙ〜３００ｋＧｙ、さらに好ましくは５０ｋＧｙ〜２５０ｋＧｙである。放射線照射によりラジカルを発生させることにより、多孔膜の基材内部のみならず、０．１μｍという小さな細孔径の細孔の側壁にも、容易にかつ均一にグラフト鎖を導入することが可能となる。ラジカル発生後、モノマーの重合反応開始まで、酸素を遮断し、多孔膜の基材のガラス転移点より低温の環境で多孔膜を保持することが望ましい。 Examples of the method for introducing graft chains into the porous membrane include a method in which radicals serving as reaction points are generated in the porous membrane, and a monomer having a double bond is polymerized using this as a base point to perform graft chain polymerization reaction. . As a method for generating radicals at this time, a method of generating radicals in the crystal components of the porous film by irradiating the porous film with radiation such as γ rays or electron beams under the condition of blocking oxygen is preferable. The irradiation dose at this time is preferably 10 kGy to 500 kGy, more preferably 20 kGy to 300 kGy, and still more preferably 50 kGy to 250 kGy. By generating radicals by radiation irradiation, it becomes possible to easily and uniformly introduce graft chains not only inside the substrate of the porous membrane but also into the side walls of pores having a small pore diameter of 0.1 μm. . It is desirable to block oxygen in the environment at a temperature lower than the glass transition point of the substrate of the porous film after the radical generation until the start of the polymerization reaction of the monomer.
多孔膜に発生させたラジカルにモノマーを重合させ、グラフト鎖の重合反応を行う際の温度は、好ましくは−１０℃〜２０℃であり、より好ましくは−１０℃〜１５℃であり、さらに好ましくは−５℃〜１０℃である。重合反応における温度が高すぎると、モノマーが多孔膜内部（基材の内部）にまで浸透しやすくなり、細孔空間内を含む多孔膜表面でなく基材の内部に固定されるグラフト鎖の比率が増加する傾向にある。一方、重合反応における温度が低すぎると、重合反応速度が著しく低下する傾向にある。モノマーがＧＭＡまたは酢酸ビニル、特にＧＭＡである場合に、上記の温度範囲でグラフト鎖の重合反応を行うことにより、全グラフト鎖のうち多孔膜の表面に固定されるグラフト鎖の割合が望ましいものとなることを本発明者らは見出している。重合反応に当たっては、モノマーを２−プロパノールまたはメタノールに溶解し、十分量の窒素気流を流すことにより、溶液内の酸素を除去する必要がある。また、モノマーの濃度は好ましくは１体積％〜２０体積％であり、より好ましくは２体積％〜１０体積％である。 The temperature at which the monomer is polymerized to radicals generated in the porous membrane and the graft chain polymerization reaction is performed is preferably -10 ° C to 20 ° C, more preferably -10 ° C to 15 ° C, and even more preferably. Is −5 ° C. to 10 ° C. If the temperature in the polymerization reaction is too high, the monomer will easily penetrate into the porous membrane (inside the base material), and the ratio of graft chains that are fixed inside the base material rather than the porous membrane surface including the pore space. Tend to increase. On the other hand, when the temperature in the polymerization reaction is too low, the polymerization reaction rate tends to be remarkably reduced. When the monomer is GMA or vinyl acetate, particularly GMA, the graft chain polymerization reaction is performed in the above temperature range, so that the ratio of the graft chain fixed to the surface of the porous membrane is desirable among all graft chains. The present inventors have found that. In the polymerization reaction, it is necessary to remove oxygen in the solution by dissolving the monomer in 2-propanol or methanol and flowing a sufficient amount of nitrogen stream. The monomer concentration is preferably 1% by volume to 20% by volume, more preferably 2% by volume to 10% by volume.
グラフト鎖への官能基の導入は、導入しようとする官能基およびグラフト鎖の種類に応じて、当業者に公知の手法を用いて行うことができる。例えば、官能基としてアニオン交換基を、グリシジルメタクリレートの重合体を含むグラフト鎖に導入する方法として、この重合体が有するエポキシ基を開環し、ジエチルアミンなどのアミンおよびジエチルアンモニウムまたはトリメチルアンモニウムなどのアンモニウム塩を付加することにより、アニオン交換基をグラフト鎖に固定することができる。官能基としてカチオン交換基または疎水性基を、グリシジルメタクリレートの重合体を含むグラフト鎖に導入する場合も同様に、この重合体が有するエポキシ基を開環し、それぞれの官能基を有する化合物と反応させることによって、所望の官能基を導入することができる。例えば、例えばカチオン交換基としてスルホン基を導入する場合には、亜硫酸ナトリウムを反応させ、疎水性基を導入する場合にはアニリン、フェノールなどを反応させて、これらの基をグラフト鎖に固定することができる。 The introduction of the functional group into the graft chain can be performed by a method known to those skilled in the art depending on the type of the functional group to be introduced and the type of graft chain. For example, as a method of introducing an anion exchange group as a functional group into a graft chain containing a polymer of glycidyl methacrylate, the epoxy group of this polymer is opened, and an amine such as diethylamine and ammonium such as diethylammonium or trimethylammonium By adding a salt, the anion exchange group can be fixed to the graft chain. Similarly, when a cation exchange group or a hydrophobic group is introduced as a functional group into a graft chain containing a polymer of glycidyl methacrylate, the epoxy group of this polymer is opened and reacted with a compound having each functional group. Thus, a desired functional group can be introduced. For example, when introducing a sulfone group as a cation exchange group, react with sodium sulfite, and when introducing a hydrophobic group, react with aniline, phenol, etc. to fix these groups to the graft chain. Can do.
グラフト鎖に対する官能基の導入率は、後述の実施例等に記載の手法を用いて測定することができる。より高い吸着容量を得るという観点からは、官能基がアニオン交換基または疎水性基である場合、グラフト鎖に対する導入率は、好ましくは２０％〜１００％、より好ましくは５０％〜１００％、更に好ましくは７０％〜１００％である。官能基がカチオン交換基である場合、グラフト鎖に対する導入率は、好ましくは１０％〜１００％、より好ましくは１５％〜１００％、更に好ましくは２０％〜１００％である。 The introduction rate of the functional group with respect to the graft chain can be measured using a method described in Examples and the like described later. From the viewpoint of obtaining a higher adsorption capacity, when the functional group is an anion exchange group or a hydrophobic group, the introduction ratio to the graft chain is preferably 20% to 100%, more preferably 50% to 100%, Preferably, it is 70% to 100%. When the functional group is a cation exchange group, the introduction ratio with respect to the graft chain is preferably 10% to 100%, more preferably 15% to 100%, and still more preferably 20% to 100%.
以下に、本実施の形態における、多孔膜を用いた、分離目的物含有溶液からの目的物の分離方法について説明する。上記の本実施の形態における多孔膜に、分離目的物を通液することにより、目的物が官能基と相互作用することによって多孔膜に吸着し、透過液から分離される。このようにして、目的物を分離することにより、分離目的物含有溶液を精製することができる。本実施の形態における多孔膜は、官能基を有するグラフト鎖が、細孔空間内を含む多孔膜表面に密に存在する。そのため、目的物の吸着が進むにつれて細孔が閉塞されれば、通液速度が減少し、好ましくは通液が停止する。これにより、目的物が透過液に漏洩することを抑制することができ、目的物を確実に分離することができる。目的物の吸着が進むにつれて細孔が閉塞されるという観点からは、目的物は粒子状の物質であることが好ましい。 Below, the separation method of the target object from the separation target object containing solution using the porous membrane in this Embodiment is demonstrated. By passing the separation target product through the porous membrane in the present embodiment, the target product is adsorbed on the porous membrane by interacting with the functional group and separated from the permeate. In this way, the target object-containing solution can be purified by separating the target object. In the porous membrane in the present embodiment, graft chains having functional groups are densely present on the porous membrane surface including the pore space. Therefore, if the pores are blocked as the adsorption of the target object proceeds, the liquid passing speed decreases, and preferably the liquid passing stops. Thereby, it can suppress that a target object leaks to a permeation | transmission liquid, and can isolate | separate a target object reliably. From the viewpoint that the pores are blocked as the adsorption of the target product proceeds, the target product is preferably a particulate substance.
上記の実施の形態において、官能基がアニオン交換基である場合、分子量数万程度の分子からサイズが数十ｎｍの粒子状の目的物、例えば、負に帯電したＤＮＡ、ウィルス、細菌、タンパク質等が分離目的物として好ましい。 In the above embodiment, when the functional group is an anion exchange group, a particulate object having a molecular weight of about several tens of thousands to several tens of nanometers, such as negatively charged DNA, virus, bacteria, protein, etc. Is preferable as a separation target.
官能基がカチオン交換基である場合も同様に、分子量数万程度の分子からサイズが数十ｎｍの粒子状の目的物、例えば、正に帯電したタンパク質、金属イオンを含む無機微粒子等が分離目的物として好ましい。 Similarly, when the functional group is a cation exchange group, a particulate object having a molecular weight of about several tens of thousands to a particle of several tens of nanometers, for example, positively charged protein, inorganic fine particles containing metal ions, etc. It is preferable as a product.
官能基が疎水性基である場合、一態様において、疎水性の性質を有する、分子量数万程度の分子からサイズが数十ｎｍの粒子状の目的物が分離目的物として好ましい。また、別の態様において、例えば疎水性基を有するグラフト鎖が固定された多孔膜をパーベーパレーション膜として用いる場合、水溶性の、分子量が数十程度以上の疎水性物質が、選択的に膜を透過させて分離するための分離目的物として好ましい。 When the functional group is a hydrophobic group, in one embodiment, a particulate target having a hydrophobic property and having a molecular weight of about several tens of thousands to a size of several tens of nanometers is preferable as the separation target. In another embodiment, for example, when a porous membrane having a graft chain having a hydrophobic group immobilized thereon is used as a pervaporation membrane, a water-soluble hydrophobic substance having a molecular weight of about several tens or more is selectively used as the membrane. It is preferable as a separation object for separation by permeation.
以下に、本実施の形態における、多孔膜を用いた、有機物−水混合溶液からの水または有機物の分離方法について、さらに説明する。上記の本実施の形態における多孔膜のうち特に官能基が疎水性基である多孔膜を介して、有機物−水混合溶液を蒸発させることにより、水または有機物が分離される。一態様において、該蒸発に際し、官能基が疎水性基である多孔膜を介して有機物が優先的に蒸発する。このような分離方法により、例えばアルコール水溶液のような、低分子の有機物と水との混合溶液を多孔膜に通液し、パーベーパレーション法、または膜蒸留法により、有機物のみを抽出し水の純度を高めることができる。官能基として疎水性基を有する多孔膜には、疎水性の高い有機物低分子が選択的に吸着される。多孔膜で隔てられた空間の一方（透過側）を減圧するなどの方法で、吸着された有機物を蒸発させることにより、空間の他方（供給側）からは多孔膜に連続的に有機物が吸着し、その結果供給側の有機物−水混合溶液から有機物が分離され、水の純度が向上する。また、透過側に蒸発した有機物蒸気を、冷却等により凝縮させて回収することにより、有機物を分離精製することもできる。すなわち、本実施の形態における多孔膜は、パーベーパレーション膜としても用いることができる。このような分離方法における有機物は、減圧等の方法で蒸発させることができるものであれば特に限定されず、例えば、アルコール、アセトン、ベンゼン、トルエン等が挙げられる。 Hereinafter, the method for separating water or organic matter from the organic matter-water mixed solution using the porous membrane in the present embodiment will be further described. Water or organic substances are separated by evaporating the organic substance-water mixed solution through the porous film whose functional group is a hydrophobic group among the porous films in the present embodiment. In one embodiment, during the evaporation, the organic matter is preferentially evaporated through the porous film whose functional group is a hydrophobic group. By such a separation method, for example, a mixed solution of a low molecular weight organic substance such as an alcohol aqueous solution and water is passed through the porous membrane, and only the organic substance is extracted by pervaporation method or membrane distillation method. Purity can be increased. Highly hydrophobic organic low molecular weight molecules are selectively adsorbed to the porous membrane having a hydrophobic group as a functional group. By evaporating the adsorbed organic matter by reducing the pressure on one side (permeation side) of the space separated by the porous membrane, the organic matter is continuously adsorbed on the porous membrane from the other side (supply side) of the space. As a result, the organic substance is separated from the organic substance-water mixed solution on the supply side, and the purity of water is improved. Moreover, organic matter can be separated and purified by condensing and recovering organic vapor evaporated on the permeate side by cooling or the like. That is, the porous film in the present embodiment can also be used as a pervaporation film. The organic substance in such a separation method is not particularly limited as long as it can be evaporated by a method such as reduced pressure, and examples thereof include alcohol, acetone, benzene, toluene and the like.
以下、参考例、実施例および比較例（本明細書中において、単に「実施例等」ともいう。）に基づいて本実施の形態をさらに具体的に説明するが、本発明の範囲は以下の実施例のみに限定されない。また、以下の全ての実施例等において、中空糸多孔膜は、基材に細孔が設けられた多孔膜である。 Hereinafter, the present embodiment will be described more specifically based on reference examples, examples, and comparative examples (also simply referred to as “examples” in the present specification), but the scope of the present invention is as follows. It is not limited only to the examples. Moreover, in all the following examples etc., a hollow fiber porous membrane is a porous membrane by which the pore was provided in the base material.
［参考例］
（１）バブルポイント法による最大細孔径の測定
中空糸多孔膜の最大細孔径を、バブルポイント法を用いて測定した。長さ８ｃｍの中空糸多孔膜の一方の末端を閉塞し、他方の末端に圧力計を介して窒素ガス供給ラインを接続した。この状態で窒素ガスを供給してライン内部を窒素に置換した後、中空糸多孔膜をエタノールに浸漬した。この時、エタノールがライン内に逆流しないように極僅かに窒素で圧力をかけた状態で、中空糸多孔膜を浸漬した。中空糸多孔膜を浸漬した状態で、窒素ガスの圧力をゆっくりと増加させ、中空糸多孔膜から窒素ガスの泡が安定して出始めた圧力Ｐを記録した。これより、最大細孔径をｄ、表面張力をγとして、下記式（Ｉ）に従って、中空糸多孔膜の最大細孔径を算出した。
ｄ＝Ｃ1γ／Ｐ・・・（Ｉ）
式（Ｉ）中、Ｃ1は定数である。エタノールを浸漬液としたときのＣ1γ＝０．６３２（ｋｇ／ｃｍ）であり、上式にＰ（ｋｇ／ｃｍ2）を代入することにより、最大細孔径ｄ（μｍ）を求めた。
[Reference example]
(1) Measurement of maximum pore diameter by bubble point method The maximum pore diameter of the hollow fiber porous membrane was measured using the bubble point method. One end of a hollow fiber porous membrane having a length of 8 cm was closed, and a nitrogen gas supply line was connected to the other end via a pressure gauge. In this state, nitrogen gas was supplied to replace the inside of the line with nitrogen, and then the hollow fiber porous membrane was immersed in ethanol. At this time, the hollow fiber porous membrane was immersed in a state where a slight pressure of nitrogen was applied so that ethanol did not flow back into the line. With the hollow fiber porous membrane immersed, the pressure of nitrogen gas was slowly increased, and the pressure P at which nitrogen gas bubbles started to stably emerge from the hollow fiber porous membrane was recorded. From this, the maximum pore diameter of the hollow fiber porous membrane was calculated according to the following formula (I), where d is the maximum pore diameter and γ is the surface tension.
d = C 1 γ / P (I)
In formula (I), C 1 is a constant. C 1 γ = 0.632 (kg / cm) when ethanol was used as the immersion liquid, and the maximum pore diameter d (μm) was determined by substituting P (kg / cm 2 ) into the above equation.
（２）透過圧力および伸張変形の測定
官能基を有するグラフト鎖を固定した１０ｃｍの中空糸多孔膜の一方の末端を漏れのないように封止した。次に、もう一方の末端から２ｍＬ／ｍｉｎの流速で、純水、緩衝液としての２０ｍｍｏｌ／ＬのＴｒｉｓ−ＨＣｌ溶液（ｐＨ８．０）、または塩溶液としての１ｍｏｌ／ＬのＮａＣｌを２０ｍｍｏｌ／ＬのＴｒｉｓ−ＨＣｌ溶液（ｐＨ８．０）に添加した溶液の３種類の溶液を通液し、このときの圧力を測定した。また、塩溶液を３０ｍＬ通液した後の中空糸多孔膜の長さを測定し、純水置換状態に対する塩溶液通液後の中空糸多孔膜の伸張変形を測定した。
(2) Measurement of permeation pressure and elongation deformation One end of a 10 cm hollow fiber porous membrane having a functional group-grafted graft chain fixed was sealed so as not to leak. Next, 20 mmol / L of pure water, 20 mmol / L Tris-HCl solution (pH 8.0) as a buffer solution, or 1 mol / L NaCl as a salt solution at a flow rate of 2 mL / min from the other end. Three types of solutions added to Tris-HCl solution (pH 8.0) were passed through, and the pressure at this time was measured. Further, the length of the hollow fiber porous membrane after passing 30 mL of the salt solution was measured, and the extension deformation of the hollow fiber porous membrane after passing the salt solution with respect to the pure water substitution state was measured.
（３）評価モジュールの作製
実施例に係る官能基を有するグラフト鎖の固定された中空糸多孔膜を３本束ね、中空糸多孔膜を閉塞しないように、ポリスルホン酸製モジュールケースにエポキシ系ポッティング剤で両末端を固定し、有効中空糸多孔膜長が３ｃｍの評価モジュールを作製した。
(3) Preparation of Evaluation Module An epoxy potting agent is placed in a module case made of polysulfonic acid so that three hollow fiber porous membranes having a graft chain having a functional group according to the embodiment are bundled and the hollow fiber porous membranes are not blocked. Then, both ends were fixed to prepare an evaluation module having an effective hollow fiber porous membrane length of 3 cm.
［実施例１］ 官能基を有するグラフト鎖が固定された多孔膜の製造
（ｉ）中空糸多孔膜へのグラフト鎖の導入
外径３．０ｍｍ、内径２．０ｍｍ、参考例（１）に記載のバブルポイント法で測定した最大細孔径が０．３μｍのポリエチレン製中空糸多孔膜を密閉容器に入れて、容器内の空気を窒素で置換した。その後、容器の外側からドライアイスで冷却しながら、γ線２００ｋＧｙを照射し、ラジカルを発生させた。得られたラジカルを有するポリエチレン製中空糸多孔膜をガラス反応管に入れて、２００Ｐａ以下に減圧することにより、反応管内の酸素を除いた。ここに５℃に調整したグリシジルメタクリレート（ＧＭＡ）５体積部、メタノール９５体積部よりなる反応液を、中空糸多孔膜の２０質量部に注入した後、２０時間密閉状態で静置して、反応温度５℃、反応液のモノマー濃度５体積％でグラフト重合反応を施し、中空糸多孔膜にグラフト鎖を導入した。なお、ＧＭＡおよびメタノールよりなる反応液は予め窒素でバブリングして、反応液内の酸素を窒素置換した。
[Example 1] Production of a porous membrane having a graft chain having a functional group fixed (i) Introduction of graft chain into hollow fiber porous membrane Outer diameter 3.0 mm, inner diameter 2.0 mm, described in Reference Example (1) A polyethylene hollow fiber porous membrane having a maximum pore diameter of 0.3 μm measured by the bubble point method was put in a sealed container, and the air in the container was replaced with nitrogen. Thereafter, while cooling with dry ice from the outside of the container, γ rays 200 kGy were irradiated to generate radicals. The obtained polyethylene hollow fiber porous membrane having radicals was put in a glass reaction tube and the pressure in the reaction tube was reduced to 200 Pa or less to remove oxygen in the reaction tube. A reaction solution consisting of 5 parts by volume of glycidyl methacrylate (GMA) adjusted to 5 ° C. and 95 parts by volume of methanol was poured into 20 parts by mass of the hollow fiber porous membrane, and then left to stand for 20 hours in a sealed state to react. A graft polymerization reaction was performed at a temperature of 5 ° C. and a monomer concentration of the reaction solution of 5% by volume to introduce a graft chain into the hollow fiber porous membrane. The reaction solution composed of GMA and methanol was previously bubbled with nitrogen to replace oxygen in the reaction solution with nitrogen.
グラフト重合反応後、反応管内の反応液を捨てた。次いで、反応管内にジメチルスルホキシドを入れて中空糸多孔膜を洗浄することにより、残存したグリシジルメタクリレート、そのオリゴマーおよび中空糸多孔膜に固定されなかったグラフト鎖を除去した。洗浄液を捨てた後、さらにジメチルスルホキシドを入れて２回洗浄を行った。次いでメタノールを用いて同様にして洗浄を３回行った。洗浄後の中空糸多孔膜を乾燥し、重量を測定したところ、中空糸多孔膜の重量はグラフト鎖導入前の２４８％であり、グラフト鎖導入前の中空糸多孔膜に対するグラフト鎖の重量の比として定義される全体のグラフト率は１４８％であった。 After the graft polymerization reaction, the reaction solution in the reaction tube was discarded. Next, dimethyl sulfoxide was placed in the reaction tube to wash the hollow fiber porous membrane, thereby removing the remaining glycidyl methacrylate, its oligomer, and the graft chain not fixed to the hollow fiber porous membrane. After discarding the washing liquid, dimethyl sulfoxide was further added and washing was performed twice. Subsequently, washing was performed three times in the same manner using methanol. The washed hollow fiber porous membrane was dried and weighed. The weight of the hollow fiber porous membrane was 248% before the graft chain was introduced, and the ratio of the weight of the graft chain to the hollow fiber porous membrane before the graft chain was introduced. The overall graft rate defined as was 148%.
また、グラフト重合反応後の中空糸多孔膜の外径は３．２６ｍｍ、内径は２．０８ｍｍであり、長さは１．０８倍に伸長していた。中空糸多孔膜の体積増加は基材内部に固定されたグラフト鎖によると考えることができるので、基材とグラフト鎖の比重は同じと仮定し、基材内部のグラフト率は下記式（ＩＩ）より３７％と算出された。
［｛［（ＯＤ1）2−（ＩＤ1）2］×Ｌ1／Ｌ0｝／｛（ＯＤ0）2−（ＩＤ0）2｝−１］×１００・・・（ＩＩ）
ここで、ＯＤ0、ＩＤ0およびＬ0はそれぞれグラフト重合反応前の中空糸多孔膜の外径、内径および長さであり、ＯＤ1、ＩＤ1およびＬ1はそれぞれグラフト重合反応後の中空糸多孔膜の外径、内径および長さである。多孔膜の細孔空間内を含む多孔膜表面に存在するグラフト鎖のグラフト率は、全体のグラフト率と基材内部のグラフト率の差より、１１１％と算出された。
The hollow fiber porous membrane after the graft polymerization reaction had an outer diameter of 3.26 mm, an inner diameter of 2.08 mm, and a length that was 1.08 times longer. Since the volume increase of the hollow fiber porous membrane can be considered to be due to the graft chain fixed inside the substrate, the specific gravity of the substrate and the graft chain is assumed to be the same, and the graft ratio inside the substrate is expressed by the following formula (II) Calculated to be 37%.
[{[(OD 1 ) 2 − (ID 1 ) 2 ] × L 1 / L 0 } / {(OD 0 ) 2 − (ID 0 ) 2 } −1] × 100 (II)
Here, OD 0 , ID 0 and L 0 are the outer diameter, inner diameter and length of the hollow fiber porous membrane before the graft polymerization reaction, and OD 1 , ID 1 and L 1 are the hollow fiber after the graft polymerization reaction, respectively. The outer diameter, inner diameter and length of the porous membrane. The graft ratio of the graft chain existing on the surface of the porous film including the pore space of the porous film was calculated as 111% from the difference between the overall graft ratio and the graft ratio inside the substrate.
以上より、グラフト重合反応によって多孔膜に固定されたグラフト鎖全てのうち、細孔空間内を含む多孔膜表面に存在するグラフト鎖の比率は７５％（＝１１１／１４８×１００）であり、基材内に存在するグラフト鎖の比率は２５％（＝３７／１４８×１００）であった。 From the above, among all the graft chains fixed to the porous membrane by the graft polymerization reaction, the ratio of the graft chains existing on the porous membrane surface including in the pore space is 75% (= 111/148 × 100). The ratio of graft chains present in the material was 25% (= 37/148 × 100).
（ｉｉ）アニオン交換基（３級アミノ基）のグラフト鎖への固定
乾燥したグラフト鎖を導入した中空糸多孔膜をメタノールに１０分以上浸漬して膨潤させた後、純水に浸漬して水置換した。ジエチルアミン５０体積部、純水５０体積部の混合溶液よりなる反応液を、上記（ｉ）で得られたグラフト反応後の中空糸多孔膜の乾燥重量に対して２０質量部、ガラス反応管に入れ、３０℃に調整した。ここに純水浸漬後のグラフト鎖を導入した中空糸多孔膜を挿入し、２１０分間静置して、グラフト鎖のエポキシ基をジエチルアミノ基に置換することにより、アニオン交換基としてジエチルアミノ基を有するグラフト鎖の固定された中空糸多孔膜を得た。得られた中空糸多孔膜は外径３．６８ｍｍ、内径２．３４ｍｍであり、中空糸多孔膜においてグラフト鎖の有するエポキシ基の８０％がジエチルアミノ基によって置換されていた。
(Ii) Fixation of anion exchange group (tertiary amino group) to graft chain After swelled by immersing a hollow fiber porous membrane into which a dried graft chain has been introduced for 10 minutes or more, it is immersed in pure water to obtain water. Replaced. A reaction solution comprising a mixed solution of 50 parts by volume of diethylamine and 50 parts by volume of pure water is placed in a glass reaction tube at 20 parts by mass with respect to the dry weight of the hollow fiber porous membrane after the graft reaction obtained in (i) above. , Adjusted to 30 ° C. A hollow fiber porous membrane into which a graft chain after immersion in pure water was introduced was inserted and allowed to stand for 210 minutes to replace the epoxy group of the graft chain with a diethylamino group, whereby a graft having a diethylamino group as an anion exchange group A hollow fiber porous membrane with a fixed chain was obtained. The obtained hollow fiber porous membrane had an outer diameter of 3.68 mm and an inner diameter of 2.34 mm. In the hollow fiber porous membrane, 80% of the epoxy groups of the graft chain were substituted with diethylamino groups.
置換率Ｔはエポキシ基のモル数Ｎ0のうち、ジエチルアミノ基に置換されたモル数をＮ1として下記式（ＩＩＩ）を用いて算出した。
Ｔ＝１００×Ｎ1／Ｎ0
＝１００×｛（ｗ1−ｗ0）／Ｍ1｝／｛ｗ0（ｄｇ／（ｄｇ＋１００））／Ｍ0｝
・・・（ＩＩＩ）
式（ＩＩＩ）中、Ｍ1はジエチルアンモニウムの分子量（７３．１４）、ｗ0はグラフト重合反応後の中空糸多孔膜の重量、ｗ1はジエチルアミノ基置換反応後の中空糸多孔膜の重量、ｄｇは全グラフト率、Ｍ0はＧＭＡの分子量（１４２）である。
The substitution rate T was calculated using the following formula (III), where N 1 was the number of moles substituted with a diethylamino group in the number of moles N 0 of the epoxy group.
T = 100 × N 1 / N 0
= 100 × {(w 1 −w 0 ) / M 1 } / {w 0 (dg / (dg + 100)) / M 0 }
... (III)
In the formula (III), M 1 is the molecular weight of diethylammonium (73.14), w 0 is the weight of the hollow fiber porous membrane after the graft polymerization reaction, w 1 is the weight of the hollow fiber porous membrane after the diethylamino group substitution reaction, dg is the total graft ratio, and M 0 is the molecular weight of GMA (142).
参考例（２）に従って、得られたアニオン交換基を有するグラフト鎖の固定された中空糸多孔膜の通液圧力および伸長変形を測定したところ、純水の通液圧は０．１２ＭＰａ、緩衝液の通液圧は０．０９ＭＰａ、塩溶液の通液圧は０．０６ＭＰａであり、塩溶液通液後の中空糸多孔膜の伸張変形は０．９％であった。 According to Reference Example (2), when the flow pressure and elongation deformation of the obtained hollow fiber porous membrane having a graft chain fixed with an anion exchange group were measured, the flow pressure of pure water was 0.12 MPa, buffer solution The solution passing pressure was 0.09 MPa, the salt solution passing pressure was 0.06 MPa, and the elongation deformation of the hollow fiber porous membrane after passing the salt solution was 0.9%.
（ｉｉｉ）カチオン交換基（スルホン基）のグラフト鎖への固定
乾燥したグラフト鎖を導入した中空糸多孔膜をメタノールに１０分以上浸漬して膨潤させた後、純水に浸漬して水置換した。亜硫酸ナトリウム１０質量部、２−プロパノール１５質量部、純水７５質量部の混合溶液よりなる反応液を、上記（ｉ）で得られたグラフト反応後の中空糸多孔膜の乾燥重量に対して２０質量部、ガラス反応管に入れ、８０℃に調整した。ここに純水浸漬後のグラフト鎖を導入した中空糸多孔膜を挿入し、３０分間静置して、グラフト鎖のエポキシ基をスルホン基に置換することにより、カチオン交換基としてスルホン基を有するグラフト鎖の固定された中空糸多孔膜を得た。得られた中空糸多孔膜は外径３．５１ｍｍ、内径２．２８ｍｍであり、中空糸多孔膜においてグラフト鎖の有するエポキシ基の３０％がスルホン基によって置換されていた。
(Iii) Fixation of cation exchange group (sulfone group) to graft chain The hollow fiber porous membrane into which the dried graft chain was introduced was immersed in methanol for 10 minutes or more to swell, and then immersed in pure water to replace with water. . A reaction solution composed of a mixed solution of 10 parts by mass of sodium sulfite, 15 parts by mass of 2-propanol, and 75 parts by mass of pure water was 20 with respect to the dry weight of the hollow fiber porous membrane after the graft reaction obtained in (i) above. The mass part was put into a glass reaction tube and adjusted to 80 ° C. A hollow fiber porous membrane into which a graft chain after immersion in pure water is introduced is inserted here, and left for 30 minutes, and the graft group having a sulfone group as a cation exchange group is substituted by a sulfone group on the graft chain. A hollow fiber porous membrane with a fixed chain was obtained. The obtained hollow fiber porous membrane had an outer diameter of 3.51 mm and an inner diameter of 2.28 mm. In the hollow fiber porous membrane, 30% of the epoxy groups of the graft chain were substituted with sulfone groups.
置換率Ｔはエポキシ基のモル数Ｎ0のうち、スルホン基に置換されたモル数をＮ2として下記式（ＩＶ）を用いて算出した。
Ｔ＝１００×Ｎ2／Ｎ0
＝１００×｛（ｗ2−ｗ0）／Ｍ2｝／｛ｗ0（ｄｇ／（ｄｇ＋１００））／Ｍ0｝
・・・（ＩＶ）
式（ＩＶ）中、Ｍ2は亜硫酸ナトリウムの分子量（１０３．０５）、ｗ0はグラフト重合反応後の中空糸多孔膜の重量、ｗ2はスルホン基置換反応後の中空糸多孔膜の重量、ｄｇは全グラフト率、Ｍ0はＧＭＡの分子量（１４２）である。
The substitution rate T was calculated by using the following formula (IV), where N 2 was the number of moles substituted with the sulfone group in the number of moles N 0 of the epoxy group.
T = 100 × N 2 / N 0
= 100 × {(w 2 −w 0 ) / M 2 } / {w 0 (dg / (dg + 100)) / M 0 }
... (IV)
In formula (IV), M 2 is the molecular weight of sodium sulfite (103.05), w 0 is the weight of the hollow fiber porous membrane after the graft polymerization reaction, w 2 is the weight of the hollow fiber porous membrane after the sulfone group substitution reaction, dg is the total graft ratio, and M 0 is the molecular weight of GMA (142).
参考例（２）に従って、得られたカチオン交換基を有するグラフト鎖の固定された中空糸多孔膜の通液圧力および伸長変形を測定したところ、純水の通液圧は０．１５ＭＰａ、緩衝液の通液圧は０．１２ＭＰａ、塩溶液の通液圧は０．１０ＭＰａであり、塩溶液通液後の中空糸多孔膜の伸張変形は０．８％であった。 According to Reference Example (2), when the flow pressure and elongation deformation of the obtained hollow fiber porous membrane having a graft chain fixed with a cation exchange group were measured, the flow pressure of pure water was 0.15 MPa, buffer solution The solution passing pressure was 0.12 MPa, the salt solution passing pressure was 0.10 MPa, and the elongation deformation of the hollow fiber porous membrane after passing the salt solution was 0.8%.
（ｉｖ）疎水性基（フェニル基）のグラフト鎖への固定
乾燥したグラフト鎖を導入した中空糸多孔膜をメタノールに１０分以上浸漬して膨潤させた後、純水に浸漬して水置換した。アニリン３質量部、水酸化ナトリウム０．４質量部、純水９７質量部の混合溶液よりなる反応液を、上記（ｉ）で得られたグラフト反応後の中空糸多孔膜の乾燥重量に対して２０質量部、ガラス反応管に入れ、３０℃に調整した。ここに純水浸漬後のグラフト鎖を導入した中空糸多孔膜を挿入し、２０時間静置して、グラフト鎖のエポキシ基をフェニル基に置換することにより、疎水性基としてフェニル基を有するグラフト鎖の固定された中空糸多孔膜を得た。得られた中空糸多孔膜は外径３．６１ｍｍ、内径２．３１ｍｍであり、中空糸多孔膜においてグラフト鎖の有するエポキシ基の７８％がフェニル基によって置換されていた。
(Iv) Fixation of hydrophobic group (phenyl group) to graft chain The hollow fiber porous membrane into which the dried graft chain was introduced was immersed in methanol for 10 minutes or more to swell, and then immersed in pure water to replace with water. . A reaction solution comprising a mixed solution of 3 parts by mass of aniline, 0.4 parts by mass of sodium hydroxide and 97 parts by mass of pure water is used with respect to the dry weight of the hollow fiber porous membrane after the graft reaction obtained in (i) above. 20 mass parts, it put into the glass reaction tube, and adjusted to 30 degreeC. A hollow fiber porous membrane into which a graft chain after immersion in pure water is introduced is inserted and allowed to stand for 20 hours to replace the epoxy group of the graft chain with a phenyl group, thereby grafting a graft having a phenyl group as a hydrophobic group. A hollow fiber porous membrane with a fixed chain was obtained. The obtained hollow fiber porous membrane had an outer diameter of 3.61 mm and an inner diameter of 2.31 mm. In the hollow fiber porous membrane, 78% of the epoxy groups of the graft chain were substituted with phenyl groups.
置換率Ｔはエポキシ基のモル数Ｎ0のうち、フェニル基に置換されたモル数をＮ3として下記式（Ｖ）を用いて算出した。
Ｔ＝１００×Ｎ3／Ｎ0
＝１００×｛（ｗ3−ｗ0）／Ｍ3｝／｛ｗ0（ｄｇ／（ｄｇ＋１００））／Ｍ0｝
・・・（Ｖ）
式（Ｖ）中、Ｍ3はアニリンの分子量（９３．１３）、ｗ0はグラフト重合反応後の中空糸多孔膜の重量、ｗ3はフェニル基置換反応後の中空糸多孔膜の重量、ｄｇは全グラフト率、Ｍ0はＧＭＡの分子量（１４２）である。
The substitution rate T was calculated using the following formula (V), where N 3 was the number of moles substituted with the phenyl group in the mole number N 0 of the epoxy group.
T = 100 × N 3 / N 0
= 100 × {(w 3 -w 0) / M 3} / {w 0 (dg / (dg + 100)) / M 0}
... (V)
In the formula (V), M 3 is the molecular weight of aniline (93.13), w 0 is the weight of the hollow fiber porous membrane after the graft polymerization reaction, w 3 is the weight of the hollow fiber porous membrane after the phenyl group substitution reaction, dg Is the total graft ratio, and M 0 is the molecular weight of GMA (142).
参考例（２）に従って、得られた疎水性基を有するグラフト鎖の固定された中空糸多孔膜の通液圧力および伸長変形を測定したところ、純水の通液圧は０．１９ＭＰａ、緩衝液の通液圧は０．２０ＭＰａ、塩溶液の通液圧は０．２１ＭＰａであり、塩溶液通液後の中空糸多孔膜の伸張変形０．６％であった。 According to Reference Example (2), when the flow pressure and elongation deformation of the obtained hollow fiber porous membrane having a hydrophobic chain having a hydrophobic group were measured, the flow pressure of pure water was 0.19 MPa, and the buffer solution The solution passage pressure was 0.20 MPa, the solution pressure of the salt solution was 0.21 MPa, and the elongation deformation of the hollow fiber porous membrane after passing the salt solution was 0.6%.
［実施例２］ アニオン交換基を有するグラフト鎖が固定された多孔膜を用いた、ＤＮＡ含有溶液からのＤＮＡの分離
参考例（３）に従って、実施例１（ｉｉ）で作成したアニオン交換基を有するグラフト鎖を固定した中空糸多孔膜のモジュールを作成した。このモジュールによる負に帯電した微粒子状物質の除去性を確認するために、和光純薬製ＤＮＡ（デオキシリボ核酸ナトリウム、サケ精巣由来、粉末、分子量３０万〜９００万）０．２ｇを２０００ｍＬの２０ｍＭ Ｔｒｉｓ−ＨＣｌ（ｐＨ８．０）緩衝液に溶解し、塩を含まない０．１ｇ／ＬのＤＮＡ溶液（ｐＨ８．０）２０００ｍＬを調整した。得られたモジュールに２０ｍＭ Ｔｒｉｓ−ＨＣｌ（ｐＨ８．０）緩衝液を２０ｍＬ通液して平衡化した後、０．３ＭＰａの一定圧力で、調整したＤＮＡ溶液を通液した。流速は最初３．７ｍＬ／ｍｉｎであったが、通液量とともに減少し、３１２ｍＬ通液したところで、流速は０ｍＬ／ｍｉｎとなり通液は停止した。通液が停止するまでに要した時間は２０８分であり、平均の流速は１．５ｍＬ／ｍｉｎであった。得られた透過液の２６０ｎｍのＵＶ吸光度を、ＧＥヘルスケア製、Ｕｌｔｒｏｓｐｅｃ２１００ｐｒｏを用いて測定したところ、吸光度は１ｍＡＵ以下であり、ＤＮＡが漏洩なく除去された透過液が得られた。
[Example 2] Separation of DNA from a DNA-containing solution using a porous membrane to which a graft chain having an anion exchange group was fixed. According to Reference Example (3), the anion exchange group prepared in Example 1 (ii) was prepared. A hollow fiber porous membrane module having a graft chain fixed thereto was prepared. In order to confirm the removability of the negatively charged particulate matter by this module, 0.2 g of Wako Pure Chemical DNA (deoxyribonucleic acid sodium, derived from salmon testis, powder, molecular weight 300,000 to 9 million) was added to 2000 mL of 20 mM Tris. -It melt | dissolved in HCl (pH 8.0) buffer solution, and prepared 2000 mL of 0.1 g / L DNA solution (pH 8.0) without a salt. After 20 mL of 20 mM Tris-HCl (pH 8.0) buffer solution was passed through the obtained module and equilibrated, the adjusted DNA solution was passed at a constant pressure of 0.3 MPa. The flow rate was initially 3.7 mL / min, but decreased with the flow rate. When 312 mL was passed, the flow rate was 0 mL / min and the flow stopped. The time required to stop the flow was 208 minutes, and the average flow rate was 1.5 mL / min. When the UV absorbance at 260 nm of the obtained permeate was measured using Ultraspec 2100pro manufactured by GE Healthcare, the absorbance was 1 mAU or less, and a permeate from which DNA was removed without leakage was obtained.
［比較例１］ アニオン交換基を有するグラフト鎖が固定された多孔膜を用いた、ＤＮＡ含有溶液からのＤＮＡの分離
グラフト重合反応温度を４０℃、反応液のモノマー濃度を１０体積％とした以外は実施例１（ｉ）および（ｉｉ）と同様にして、アニオン交換基を有するグラフト鎖を固定した中空糸多孔膜を作成した。得られた中空糸多孔膜は、全グラフト率１５８％、細孔空間内を含む多孔膜表面に存在するグラフト鎖は全体の２７％、基材内に存在するグラフト鎖は全体の７３％であり、アニオン交換基によってグラフト鎖の有するエポキシ基の８２％が置換され、また、得られた中空糸多孔膜は外径４．１ｍｍ、内径２．６ｍｍであった。参考例（２）に従って、得られたアニオン交換基を有するグラフト鎖の固定された中空糸多孔膜の通液圧力および伸長変形を測定したところ、純水の通液圧は０．０２ＭＰａ、緩衝液の通液圧は０．０３ＭＰａ、塩溶液の通液圧は０．０２ＭＰａであり、塩溶液通液後の中空糸多孔膜の伸張変形は８．２％であった。得られた中空糸多孔膜を用いて、実施例２と同様にしてモジュールを作成し、０．３ＭＰａの一定圧力でＤＮＡ溶液を通液したところ、通液の停止はなく、平均流速８．７ｍＬ／ｍｉｎで２０００ｍＬのＤＮＡ溶液を全て通液した。得られた透過液の２６０ｎｍのＵＶ吸光度を測定したところ、２０２ｍＡＵであり、０．１ｍｇ／ｍＬのＵＶ吸光度２７０ｍＡＵから、透過液中のＤＮＡ濃度は０．０７５ｍｇ／ｍＬと求められた。これより、グラフト反応温度４０℃にて作成した、アニオン交換基を有するグラフト鎖の固定された中空糸多孔膜は、ＤＮＡ吸着性はあるものの、破過後にＤＮＡが漏洩していることが確認された。
[Comparative Example 1] Separation of DNA from DNA-containing solution using a porous membrane to which a graft chain having an anion exchange group was fixed Except that the graft polymerization reaction temperature was 40 ° C and the monomer concentration of the reaction solution was 10% by volume. Produced a hollow fiber porous membrane in which a graft chain having an anion exchange group was fixed in the same manner as in Examples 1 (i) and (ii). The obtained hollow fiber porous membrane has a total graft ratio of 158%, graft chains existing on the surface of the porous membrane including the pore space, 27% of the total, and graft chains existing in the base material of 73% of the total. 82% of the epoxy groups of the graft chain were replaced by anion exchange groups, and the obtained hollow fiber porous membrane had an outer diameter of 4.1 mm and an inner diameter of 2.6 mm. According to Reference Example (2), when the flow pressure and elongation deformation of the obtained hollow fiber porous membrane having a graft chain fixed with an anion exchange group were measured, the flow pressure of pure water was 0.02 MPa, buffer solution The solution passing pressure was 0.03 MPa, the salt solution passing pressure was 0.02 MPa, and the elongation deformation of the hollow fiber porous membrane after passing the salt solution was 8.2%. Using the obtained hollow fiber porous membrane, a module was prepared in the same manner as in Example 2, and when the DNA solution was passed at a constant pressure of 0.3 MPa, the passing was not stopped and the average flow rate was 8.7 mL. All of the 2000 mL DNA solution was passed at / min. The UV absorbance at 260 nm of the obtained permeate was measured and found to be 202 mAU. From the UV absorbance of 270 mAU at 0.1 mg / mL, the DNA concentration in the permeate was determined to be 0.075 mg / mL. From this, it was confirmed that the hollow fiber porous membrane prepared with a graft reaction temperature of 40 ° C. and having a graft chain having an anion exchange group fixed has DNA adsorbability, but DNA has leaked after breakthrough. It was.
［実施例３］ カチオン交換基を有するグラフト鎖が固定された多孔膜を用いた、タンパク質含有溶液からのタンパク質の分離
参考例（３）に従って、実施例１（ｉｉｉ）で作成したカチオン交換基を有するグラフト鎖を固定した中空糸多孔膜のモジュールを作成した。このモジュールによる正に帯電した微粒子状物質の除去性を確認するために、シグマ製リゾチーム（分子量１４．４万）１．０ｇを１０００ｍＬの２０ｍＭ Ｔｒｉｓ−ＨＣｌ（ｐＨ８．０）緩衝液に溶解し、塩を含まない１．０ｇ／Ｌのリゾチーム溶液（ｐＨ８．０）２０００ｍＬを調整した。得られたモジュールに２０ｍＭ Ｔｒｉｓ−ＨＣｌ（ｐＨ８．０）緩衝液を２０ｍＬ通液して平衡化した後、０．３ＭＰａの一定圧力で、調整したＤＮＡ溶液を通液した。流速は最初２．５ｍＬ／ｍｉｎであったが、通液量とともに減少し、１６８ｍＬ通液したところで、流速は０ｍＬ／ｍｉｎとなり通液は停止した。通液が停止するまでに要した時間は１８７分であり、平均の流速は０．９ｍＬ／ｍｉｎであった。得られた透過液の２８０ｎｍのＵＶ吸光度を、ＧＥヘルスケア製、Ｕｌｔｒｏｓｐｅｃ２１００ｐｒｏを用いて測定したところ、吸光度は１ｍＡＵ以下であり、リゾチームが漏洩なく除去された透過液が得られた。
[Example 3] Separation of a protein from a protein-containing solution using a porous membrane to which a graft chain having a cation exchange group is fixed The cation exchange group prepared in Example 1 (iii) according to Reference Example (3) A hollow fiber porous membrane module having a graft chain fixed thereto was prepared. In order to confirm the removability of positively charged particulate matter by this module, 1.0 g of Sigma lysozyme (molecular weight: 144,000) was dissolved in 1000 mL of 20 mM Tris-HCl (pH 8.0) buffer, A salt-free 1.0 g / L lysozyme solution (pH 8.0) 2000 mL was prepared. After 20 mL of 20 mM Tris-HCl (pH 8.0) buffer solution was passed through the obtained module and equilibrated, the adjusted DNA solution was passed at a constant pressure of 0.3 MPa. Initially, the flow rate was 2.5 mL / min, but decreased with the flow rate. When 168 mL was passed, the flow rate was 0 mL / min and the flow stopped. The time required to stop the flow was 187 minutes, and the average flow rate was 0.9 mL / min. When the UV absorbance at 280 nm of the obtained permeate was measured using Ultraspec 2100pro manufactured by GE Healthcare, the absorbance was 1 mAU or less, and a permeate from which lysozyme was removed without leakage was obtained.
［実施例４］ 疎水性基を有するグラフト鎖が固定された多孔膜を用いた、パーベーパレーション
参考例（３）に従って、実施例１（ｉｖ）で作成した疎水性基を有するグラフト鎖を固定した中空糸多孔膜のモジュールを作成した。このモジュールの、中空糸多孔膜内径および中空糸多孔膜長から求めた中空糸多孔膜内側の膜面積は６．５ｃｍ2であった。エタノール６質量部と純水９４質量部からなる混合液１００ｍＬを調整し、これを４０℃に保持して中空糸多孔膜の内側の片端から供給し、もう一方の片端から取り出すように通液してモジュール内を２０ｍＬ／ｍｉｎで循環させた。中空糸多孔膜の外側のモジュール内を真空ポンプに接続して減圧し、モジュールと真空ポンプの間に液体窒素で冷却したトラップを取付けて、減圧により中空糸多孔膜の外側から揮発した成分をトラップした。３０分間この状態を継続した後、トラップした透過成分の質量を測定したところ、５．８９ｇであり、このエタノール濃度をガスクロマトグラフィーにより測定したところ、７６．１質量％であった。これよりパーベーパレーション膜として評価した中空糸多孔膜の透過流速は１８．２ｋｇ／ｍ2ｈであり、また供給側のエタノールと水の重量濃度をそれぞれ、Ｘ1重量％、Ｘ2重量％とし、トラップ中の透過側のエタノールと水の濃度をそれぞれ、Ｙ1重量％、Ｙ2重量％として、α＝（Ｘ2／Ｘ1）／（Ｙ2／Ｙ1）によって計算される分離係数は、１９５であった。
[Example 4] Pervaporation using a porous membrane on which a graft chain having a hydrophobic group is fixed According to Reference Example (3), a graft chain having a hydrophobic group prepared in Example 1 (iv) is fixed. A hollow fiber porous membrane module was prepared. The membrane area of the inside of the hollow fiber porous membrane obtained from the hollow fiber porous membrane inner diameter and hollow fiber porous membrane length of this module was 6.5 cm 2 . 100 mL of a mixed solution consisting of 6 parts by mass of ethanol and 94 parts by mass of pure water was prepared, and this was maintained at 40 ° C., supplied from one end inside the hollow fiber porous membrane, and passed through so as to be taken out from the other end. The module was circulated at 20 mL / min. The module outside the hollow fiber porous membrane is connected to a vacuum pump to reduce the pressure, and a trap cooled with liquid nitrogen is attached between the module and the vacuum pump to trap the components volatilized from the outside of the hollow fiber porous membrane due to the reduced pressure. did. After this state was continued for 30 minutes, the mass of the trapped permeation component was measured and found to be 5.89 g. The ethanol concentration measured by gas chromatography was 76.1% by mass. From this, the permeation flow rate of the hollow fiber porous membrane evaluated as a pervaporation membrane was 18.2 kg / m 2 h, and the weight concentrations of ethanol and water on the supply side were X 1 wt% and X 2 wt%, respectively. The separation factor calculated by α = (X 2 / X 1 ) / (Y 2 / Y 1 ) where the concentrations of ethanol and water on the permeate side in the trap are Y 1 wt% and Y 2 wt%, respectively. 195.
本発明の官能基を有するグラフト鎖が固定された多孔膜は形状安定性に優れ、また該多孔膜を用いることにより、目的物の漏洩なく除去することが可能となるという産業上の利用可能性を有する。また、前記官能基が疎水性基である多孔膜は水と有機物の混合物を膜蒸留や浸透気化により分離するパーベーパレーション膜としての産業上の利用可能性も有する。 Industrial applicability that the porous membrane with a graft chain having a functional group of the present invention is excellent in shape stability, and that the porous membrane can be removed without leakage of the target product. Have Moreover, the porous membrane in which the functional group is a hydrophobic group also has industrial applicability as a pervaporation membrane that separates a mixture of water and organic matter by membrane distillation or pervaporation.
Claims (8)
前記グラフト鎖の少なくとも３０％以上が、前記多孔膜の表面に固定されている、多孔膜。 A porous membrane to which a graft chain having a functional group is fixed,
A porous membrane in which at least 30% or more of the graft chains are fixed on the surface of the porous membrane.
グラフト鎖に官能基を導入する工程；
を含む、官能基を有するグラフト鎖が固定された多孔膜の製造方法。 A step of introducing a graft chain into a porous membrane having a maximum pore size of 0.1 μm to 1.0 μm and a porosity of 50% to 95% by conducting a polymerization reaction of the graft chain at −10 ° C. to 20 ° C .; and grafting Introducing a functional group into the chain;
The manufacturing method of the porous film by which the graft chain which has a functional group containing was fixed.
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| WO2013133043A1 (en) * | 2012-03-09 | 2013-09-12 | 日東電工株式会社 | Method for separating oil and water, method for processing oil-containing water, method for producing bitumen, and system thereof |
| WO2015080125A1 (en) * | 2013-11-27 | 2015-06-04 | 住友電気工業株式会社 | Membrane distillation module and waste water treatment device |
| WO2015080123A1 (en) * | 2013-11-27 | 2015-06-04 | 住友電気工業株式会社 | Waste water treatment method, membrane distillation module, and waste water treatment device |
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| WO2013133043A1 (en) * | 2012-03-09 | 2013-09-12 | 日東電工株式会社 | Method for separating oil and water, method for processing oil-containing water, method for producing bitumen, and system thereof |
| JP2013185127A (en) * | 2012-03-09 | 2013-09-19 | Nitto Denko Corp | Method for separating oil and water, method for processing oil-containing water, method for producing bitumen, and system thereof |
| WO2015080125A1 (en) * | 2013-11-27 | 2015-06-04 | 住友電気工業株式会社 | Membrane distillation module and waste water treatment device |
| WO2015080123A1 (en) * | 2013-11-27 | 2015-06-04 | 住友電気工業株式会社 | Waste water treatment method, membrane distillation module, and waste water treatment device |
| JP2015100777A (en) * | 2013-11-27 | 2015-06-04 | 住友電気工業株式会社 | Membrane distillation module and waste water processing apparatus |
| WO2015080124A1 (en) * | 2013-11-27 | 2015-06-04 | 住友電気工業株式会社 | Wastewater treatment method, membrane distillation module and wastewater treatment apparatus |
| WO2016175306A1 (en) * | 2015-04-30 | 2016-11-03 | 昭和電工株式会社 | Protein purification method |
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