JP2006247515A

JP2006247515A - Monolith capillary column made of organic polymer and its production method

Info

Publication number: JP2006247515A
Application number: JP2005066929A
Authority: JP
Inventors: Akio Katagai; 秋雄片貝; Masao Tamada; 正男玉田; Kinichi Tsunoda; 欣一角田; Tomoya Umemura; 知也梅村
Original assignee: Nagoya University NUC; Gunma University NUC; Japan Atomic Energy Agency
Current assignee: Nagoya University NUC; Gunma University NUC; Japan Atomic Energy Agency
Priority date: 2005-03-10
Filing date: 2005-03-10
Publication date: 2006-09-21
Anticipated expiration: 2025-03-10
Also published as: JP4836167B2

Abstract

<P>PROBLEM TO BE SOLVED: To synthesize a monolith column made of an organic polymer by a radiation induced copolymerization method in place of the production method of a radical polymerization method using a conventional initiator. <P>SOLUTION: In a fused silica capillary tube, (1) hexyl methacrylate and ethyleneglycol dimethacrylate to be a crosslinking agent, or (2) glycidyl methacrylate and ethyleneglycol dimethacrylate to be the crosslinking agent are subjected to the radiation induced copolymerization under the presence of 1-propanol, 1,4-butanediol and a mixed solvent of water using Co-60 γ radiation at a room temperature (25°C). <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

本発明は、放射線重合法により、溶融シリカキャピラリー管内に、メタクリル酸ヘキシルと架橋剤のジメタクリル酸エチレングリコール、又はメタクリル酸グリシジルと架橋剤のジメタクリル酸エチレングリコールとを、１−プロパノール、１，４−ブタンジオール、及び水の混合溶媒に溶かしたモノマー溶液を充填した後、Ｃｏ−６０γ線を用いて放射線共重合した、芳香族化合物の疎水性相互作用の違いにより分離し、及び共重合後、陽イオン交換基を導入して陽イオン交換を行うモノリスゲルを有する有機ポリマー製モノリスキャピラリーカラム及びその製造方法である。 In the fused silica capillary tube according to the present invention, hexyl methacrylate and ethylene glycol dimethacrylate as a crosslinking agent, or glycidyl methacrylate and ethylene glycol dimethacrylate as a crosslinking agent are mixed with 1-propanol, 1, After charging with a monomer solution dissolved in a mixed solvent of 4-butanediol and water, it was separated by the difference in the hydrophobic interaction of the aromatic compound, which was subjected to radiation copolymerization using Co-60γ rays, and after the copolymerization An organic polymer monolith capillary column having a monolith gel for introducing a cation exchange group to perform cation exchange and a method for producing the same.

即ち、本発明は、複数の芳香族化合物をそれらの疎水性相互作用の違いにより分離することのできる、モノマーと架橋剤モノマーからなる2種類のモノマーを放射線共重合させて得られたモノリスゲルを有する有機ポリマー製モノリスキャピラリーカラム及びその製造方法に関するものである。上記モノリスゲルとは、重合によって生成した粒子と粒子の間が結合している状態、又はその粒子がブドウの房状の形態をしているものである。 That is, the present invention has a monolith gel obtained by radiation copolymerization of two types of monomers consisting of a monomer and a crosslinking agent monomer, which can separate a plurality of aromatic compounds by the difference in their hydrophobic interaction. The present invention relates to an organic polymer monolith capillary column and a method for producing the same. The monolith gel is a state in which particles produced by polymerization are bonded to each other, or the particles are in the form of a tuft of grapes.

又、本発明は、モノマーと架橋剤モノマーからなる2種類のモノマーを放射線共重合させた後に、陽イオン交換基を導入した陽イオン交換を行うことのできるモノリスゲルを有する有機ポリマー製モノリスキャピラリーカラム及びその製造方法に関するものである。前記カラムは、複数種類の芳香族化合物の疎水性相互作用の違いにより、それぞれの芳香族化合物を分離することに使用される。 The present invention also provides an organic polymer monolith capillary column having a monolith gel capable of performing cation exchange in which a cation exchange group is introduced after radiation copolymerization of two types of monomers comprising a monomer and a cross-linking agent monomer. It relates to a manufacturing method. The column is used to separate each aromatic compound due to a difference in hydrophobic interaction among a plurality of types of aromatic compounds.

Conventional technology

分離分析の分野では、分析時間の高速化への要求が強まっているが、粒子状の分離媒体を充填する従来のカラムでは、カラム背圧の増加や理論段数の低下を抑えることができずその改善が望まれていた。この問題を解決するためには、連続多孔質分離媒体（モノリス）を有する低背圧カラムの構築が必要である。その一つとして、モノリスをカラム管内で直接合成することができ、かつモノマーの種類が豊富で多様な分離選択性の創出が容易な開始剤を用いたラジカル重合法による有機ポリマー製モノリスカラムが知られている（非特許文献１，２）。
Journal of Chromatography A, 946(2002)99-106 Nuclear Instrument and Metals in Physics Research B 185(254-261) In the field of separation analysis, there is an increasing demand for faster analysis time, but conventional columns packed with particulate separation media cannot suppress an increase in column back pressure or a decrease in the number of theoretical plates. Improvement was desired. In order to solve this problem, it is necessary to construct a low back pressure column with a continuous porous separation medium (monolith). One of them is a monolithic column made of organic polymer by radical polymerization using an initiator that can synthesize monoliths directly in a column tube and has a wide variety of monomers and can easily create diverse separation selectivity. (Non-Patent Documents 1 and 2).
Journal of Chromatography A, 946 (2002) 99-106 Nuclear Instrument and Metals in Physics Research B 185 (254-261)

本発明の課題は、連続多孔質分離媒体（モノリス）を有する低背圧カラムを構成するモノリスをカラム管内で直接合成する方法において、従来の開始剤を用いたラジカル重合法の製法に代えて、放射線照射共重合法により有機ポリマー製モノリスカラムを合成することである。 The subject of the present invention is a method of directly synthesizing a monolith constituting a low back pressure column having a continuous porous separation medium (monolith) in a column tube, instead of a conventional radical polymerization method using an initiator, It is to synthesize an organic polymer monolith column by a radiation irradiation copolymerization method.

本発明の有機ポリマー製モノリスキャピラリーカラムは、溶融シリカキャピラリー管内に、（１）メタクリル酸ヘキシル及び架橋剤のジメタクリル酸エチレングリコール、又は（２）メタクリル酸グリシジル及び架橋剤のジメタクリル酸エチレングリコールを、１−プロパノール、１，４−ブタンジオール及び水の混合溶媒の存在下でＣｏ−６０γ線を用いて室温（２５℃）で放射線共重合して得られたものである。 The organic polymer monolith capillary column of the present invention contains (1) hexyl methacrylate and ethylene glycol dimethacrylate as a crosslinking agent, or (2) glycidyl methacrylate and ethylene glycol dimethacrylate as a crosslinking agent, in a fused silica capillary tube. It was obtained by radiation copolymerization at room temperature (25 ° C.) using Co-60γ rays in the presence of a mixed solvent of 1-propanol, 1,4-butanediol and water.

本発明によれば、溶融シリカキャピラリー管内にモノマー溶液を充填し、室温(２５℃）にて短時間の放射線共重合により粒子径が小さく、且つ単分散のモノリスゲルを有する有機ポリマー製モノリスキャピラリーカラムが開発された。さらに、モノリスゲル作製時のモノマー濃度を調製することによってカラム背圧が低く、理論段数の高いモノリスキャピラリーカラムを効率よく作製することができる。 According to the present invention, a monolithic capillary column made of an organic polymer having a monodispersed monolithic gel with a small particle diameter is developed by filling a fused silica capillary tube with a monomer solution at a room temperature (25 ° C.) for a short time by radiation copolymerization. It was done. Furthermore, by adjusting the monomer concentration at the time of monolith gel production, a monolith capillary column having a low column back pressure and a high theoretical plate number can be produced efficiently.

Best Mode for Carrying Out the Invention

本発明で行われる放射線重合法は、室温（０〜２５℃）において短時間（約1時間前後）で重合が完結することを特徴とするものである。従って、本発明においては、従来の技術では困難であった重合時間の短縮化や重合温度の低減化の課題が克服でき、粒子径が小さく、且つ単分散のモノリスゲルを有する有機ポリマー製モノリスキャピラリーカラムを合成することができる。 The radiation polymerization method performed in the present invention is characterized in that the polymerization is completed in a short time (about 1 hour) at room temperature (0 to 25 ° C.). Therefore, in the present invention, an organic polymer monolith capillary column having a monodispersed monolith gel having a small particle size and capable of overcoming the problems of shortening the polymerization time and lowering the polymerization temperature, which has been difficult with the prior art. Can be synthesized.

（実施例１）
内径０．２５ｍｍの溶融シリカキャピラリー管内壁表面を、モノリスゲルが抜け落ちないようにするために、モノマー及びガラスの両方に結合部位を持つ３−メタクリロキシプロピルトリメトキシシランにより６０℃で２４時間処理した後、メタクリル酸ヘキシル（ＨＭＡ）と架橋剤のジメタクリル酸エチレングリコール（ＥＤＭＡ）（２５％）を１−プロパノール、１，４−ブタンジオール、水の混合溶媒に溶かしたモノマー濃度４０％の反応溶液を３分間窒素バブリングした。 Example 1
After treating the inner wall surface of a fused silica capillary tube having an inner diameter of 0.25 mm with 3-methacryloxypropyltrimethoxysilane having a binding site on both monomer and glass at 60 ° C. for 24 hours in order to prevent the monolith gel from falling off. A reaction solution having a monomer concentration of 40% prepared by dissolving hexyl methacrylate (HMA) and ethylene glycol dimethacrylate methacrylate (EDMA) (25%) in a mixed solvent of 1-propanol, 1,4-butanediol and water. Nitrogen was bubbled for 3 minutes.

このモノマー溶液を前処理した溶融シリカキャピラリー管内に充填した後、両端をシリコン栓で密封し、室温（２５℃）で線量率１０ｋＧｙ／ｈのＣｏ−６０γ線を１時間照射してモノリスゲルを作製した。 After filling this monomer solution into a pretreated fused silica capillary tube, both ends were sealed with silicon stoppers and irradiated with Co-60γ rays at a dose rate of 10 kGy / h for 1 hour at room temperature (25 ° C.) to prepare a monolith gel. .

このようにして得られたモノリスキャピラリーカラムを用いて、アセトフェノン、ニトロベンゼン、ナフタレンの芳香族化合物の疎水性相互作用の違いによる分離を行った。３成分の保持挙動（図１；図中、Ｔは溶媒に対する全モノマー濃度を示す。）は、比較例で示す熱重合法により作製したモノリスキャピラリーカラムのそれ（図3）と良く一致し、線量率１０ｋＧｙ／ｈで１時間重合することによって十分な分離性能を有するモノリスキャピラリーカラムを得た。
（実施例２）
実施例１と同様な方法で、表１（モノリスカラム作製時のモノマー溶液の組成）に示す各モノマー濃度の反応溶液を用いて、よりカラム背圧の低いモノリスキャピラリーカラムを作製した。このようにして得られたモノリスキャピラリーカラムを用いて、アセトフェノン、ニトロベンゼン、ナフタレンの芳香族化合物の分離を行った。送液度１ｍｍ／ｓ（流速：３μＬ／ｍｉｎ）の時のカラム背圧は、図２のようにモノマー濃度４０％で４．０ＭＰａ、１０％で０．５ＭＰａであった。モノマー濃度２０％以下のモノリスカラムではカラム背圧が２．０ＭＰａ以下となり、市販のＨＰＬＣ（高速液体クロマトグラフィー）用ポンプでも十分に高速分離が可能なモノリスカラムを得た。この時の理論段数は、１５００段／１８０ｍｍであり、比較例で示す熱重合法のカラム（モノマー濃度４０％）の３倍であった。 The monolith capillary column thus obtained was used to separate the aromatic compounds of acetophenone, nitrobenzene, and naphthalene based on the difference in hydrophobic interaction. The retention behavior of the three components (FIG. 1; in the figure, T indicates the total monomer concentration with respect to the solvent) agrees well with that of the monolith capillary column prepared by the thermal polymerization method shown in the comparative example (FIG. 3), and the dose rate A monolith capillary column having sufficient separation performance was obtained by polymerization at 10 kGy / h for 1 hour.
(Example 2)
In the same manner as in Example 1, monolithic capillary columns with lower column back pressure were produced using the reaction solutions having the respective monomer concentrations shown in Table 1 (composition of monomer solution when producing monolithic column). Using the monolith capillary column thus obtained, aromatic compounds such as acetophenone, nitrobenzene and naphthalene were separated. The column back pressure at a liquid feed rate of 1 mm / s (flow rate: 3 μL / min) was 4.0 MPa at a monomer concentration of 40% and 0.5 MPa at 10% as shown in FIG. With a monolithic column having a monomer concentration of 20% or less, the column back pressure was 2.0 MPa or less, and a monolithic column capable of sufficiently separating at a high speed was obtained with a commercially available HPLC (high performance liquid chromatography) pump. The number of theoretical plates at this time was 1500 plates / 180 mm, which was three times that of the column (monomer concentration 40%) of the thermal polymerization method shown in the comparative example.

上記表中、Ｃ１〜Ｃ５はサンプルのロットナンバーであり、Ｔは溶媒に対する全モノマー濃度を示す。
（比較例１）
メタクリル酸ヘキシル（３００μＬ）と架橋剤のジメタクリル酸エチレングリコール（１００μＬ）を１−プロパノール（３５０μＬ）、１，４−ブタンジオール（２００μＬ）、水（５０μＬ）の混合溶媒に溶かしたモノマー濃度４０％の反応溶液を３分間窒素バブリングした後、重合開始剤である２，２−アゾイソブチロニトリル（４ｍｇ）を添加した。このモノマー濃度４０％の溶液を前処理した溶融シリカキャピラリー管内に充填した後、両端をシリコン栓で密封し、反応温度６０℃で２４時間重合した。 In the above table, C1 to C5 are sample lot numbers, and T represents the total monomer concentration relative to the solvent.
(Comparative Example 1)
Monomer concentration 40% in which hexyl methacrylate (300 μL) and ethylene glycol dimethacrylate (100 μL) as a crosslinking agent are dissolved in a mixed solvent of 1-propanol (350 μL), 1,4-butanediol (200 μL) and water (50 μL) After bubbling with nitrogen for 3 minutes, 2,2-azoisobutyronitrile (4 mg) as a polymerization initiator was added. This solution with a monomer concentration of 40% was filled in a pretreated fused silica capillary tube, and then sealed at both ends with silicon stoppers, and polymerized at a reaction temperature of 60 ° C. for 24 hours.

このようにして得られたモノリスキャピラリーカラムを用いて、アセトフェノン、ニトロベンゼン、ナフタレンの芳香族化合物の疎水性相互作用の違いによる分離を行い、図３に示す３成分の保持挙動を得た。この時の理論段数は、５００段／１８ｍｍであった。 Using the monolith capillary column thus obtained, separation was performed by the difference in hydrophobic interaction of aromatic compounds of acetophenone, nitrobenzene, and naphthalene, and the retention behavior of the three components shown in FIG. 3 was obtained. The number of theoretical plates at this time was 500 plates / 18 mm.

Industrial application fields

有機ポリマー製モノリスキャピラリーカラムは、モノマーの種類が豊富で目的に応じたモノマー系を選択でき、多様な分離選択性の創出が容易であること、適用可能なｐＨ範囲が２〜１２と広く、固定相の化学修飾が容易であるなどの特徴を持ち、多様な分離選択性と適応性を併せ持つカラムの創製が期待される。本発明の放射線重合法で作製した高分離性有機ポリマー製モノリスキャピラリーカラムによってこれらの課題を解決することが可能となる。 Monolithic capillary columns made of organic polymers have many types of monomers and can select the monomer system according to the purpose, easily create a variety of separation selectivity, and have a wide applicable pH range of 2-12. It is expected to create a column that has various characteristics such as easy chemical modification and has various separation selectivity and adaptability. These problems can be solved by the monolithic capillary column made of a highly separable organic polymer produced by the radiation polymerization method of the present invention.

本発明の放射線重合により作製したモノリスカラムによる芳香族化合物の分離形態を示す図である。It is a figure which shows the isolation | separation form of the aromatic compound by the monolith column produced by the radiation polymerization of this invention. 本発明のモノマー濃度とカラム背圧の関係を示す図である。It is a figure which shows the relationship between the monomer concentration of this invention, and column back pressure. 熱重合により作製したモノリスカラムによる芳香族化合物の分離形態を示す図である。It is a figure which shows the isolation | separation form of the aromatic compound by the monolithic column produced by thermal polymerization.

Claims

An organic polymer monolith capillary column composed of a monolith gel obtained by radiation copolymerization of two types of monomers and performing cation exchange by introduction of a cation exchange group, and separation by the difference in hydrophobic interaction of aromatic compounds.

A method for producing an organic polymer monolith capillary column comprising a monolith gel obtained by filling a fused silica capillary tube with a solution in which two types of monomers are dissolved in a mixed solvent, followed by radiation copolymerization.

The production method according to claim 2, wherein hexyl methacrylate-ethylene glycol methacrylate and glycidyl methacrylate-ethylene glycol glycol are used as monomers.

The production method according to claim 2, comprising three components of 1-propanol, 1,4-butanediol and water as a mixed solvent.

The manufacturing method according to claim 2, wherein Co-60 γ rays are used as a radiation source.

The process according to claim 2, wherein the reaction temperature is from 0C to room temperature (25C).

The production method according to claim 2, wherein the column back pressure is adjusted by changing the monomer concentration to 10 to 40% by volume.