JP2022064159A - Plastic molding used in biotechnology field and production thereof - Google Patents
Plastic molding used in biotechnology field and production thereof Download PDFInfo
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- 238000004519 manufacturing process Methods 0.000 title claims description 12
- 238000010137 moulding (plastic) Methods 0.000 title abstract 3
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 claims abstract description 53
- 238000000465 moulding Methods 0.000 claims abstract description 48
- 229920006026 co-polymeric resin Polymers 0.000 claims abstract description 38
- 239000004033 plastic Substances 0.000 claims abstract description 37
- 229920003023 plastic Polymers 0.000 claims abstract description 37
- 239000000463 material Substances 0.000 claims abstract description 26
- 238000004458 analytical method Methods 0.000 claims abstract description 19
- 229920001169 thermoplastic Polymers 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims description 27
- 238000001816 cooling Methods 0.000 claims description 17
- 239000004416 thermosoftening plastic Substances 0.000 claims description 9
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- 229920000642 polymer Polymers 0.000 abstract description 7
- 239000000654 additive Substances 0.000 abstract description 5
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- 229910052710 silicon Inorganic materials 0.000 abstract description 4
- 239000010703 silicon Substances 0.000 abstract description 2
- 238000012360 testing method Methods 0.000 description 39
- 238000005259 measurement Methods 0.000 description 34
- -1 siloxane) part Chemical group 0.000 description 22
- 108090000623 proteins and genes Proteins 0.000 description 19
- 229920005989 resin Polymers 0.000 description 19
- 239000011347 resin Substances 0.000 description 19
- 239000004743 Polypropylene Substances 0.000 description 18
- 238000001179 sorption measurement Methods 0.000 description 17
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 16
- 229920001155 polypropylene Polymers 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 12
- 238000001125 extrusion Methods 0.000 description 11
- 230000008859 change Effects 0.000 description 10
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- 238000004833 X-ray photoelectron spectroscopy Methods 0.000 description 8
- 229940098773 bovine serum albumin Drugs 0.000 description 8
- 235000011187 glycerol Nutrition 0.000 description 8
- 235000015112 vegetable and seed oil Nutrition 0.000 description 8
- 239000008158 vegetable oil Substances 0.000 description 8
- 238000001746 injection moulding Methods 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 6
- 239000012535 impurity Substances 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
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- 229920000620 organic polymer Polymers 0.000 description 4
- 239000005871 repellent Substances 0.000 description 4
- 238000010276 construction Methods 0.000 description 3
- 239000000498 cooling water Substances 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
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- 230000008569 process Effects 0.000 description 3
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- 239000004417 polycarbonate Substances 0.000 description 2
- 230000001172 regenerating effect Effects 0.000 description 2
- 238000004544 sputter deposition Methods 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
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- 230000003247 decreasing effect Effects 0.000 description 1
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- 229910052731 fluorine Inorganic materials 0.000 description 1
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- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
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- 230000001376 precipitating effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
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- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Injection Moulding Of Plastics Or The Like (AREA)
Abstract
Description
本発明は、遺伝子分析（ＰＣＲ）、細胞培養等のバイオテクノロジ分野で用いられるプラスチック成形品及びその製造方法に関するものである。 The present invention relates to a plastic molded product used in the field of biotechnology such as gene analysis (PCR) and cell culture, and a method for producing the same.
遺伝子分析、各種医療・創薬における細胞培養等の分野において使用されるプラスチック成形品からなるシングルユース製品（使い捨て製品）は、一般的に不純物（コンタミ）を含有しない透明でナチュラルベースのプラスチック材料が用いられている。
透明であるのは、肉眼における視認性と顕微鏡等による光学分析に対応するためであり、不純物を嫌うのは分析する上での弊害をより少なくし、分析・培養対象である細胞に害を与える可能性をより低くするという目的がある。それゆえ、これらの製品は純粋な素材をクリーンな環境で加工するというプロセスで生産されてきた。
Single-use products (disposable products) consisting of plastic molded products used in fields such as gene analysis and cell culture in various medical and drug discovery are generally transparent, natural-based plastic materials that do not contain impurities (contamination). It is used.
The reason why it is transparent is that it is visible to the naked eye and corresponds to optical analysis with a microscope, etc., and dislike of impurities reduces the harmful effects on analysis and damages the cells to be analyzed and cultured. The purpose is to make it less likely. Therefore, these products have been produced in the process of processing pure materials in a clean environment.
しかし、分析技術・培養技術の高度化により製品の高度化が求められるようになり、遺伝子・血液においては、より少ない試料で正確な解析を、再生医療・創薬においては、均一でバラツキがなく歩留まりの高い細胞培養プロセスのニーズが高まっている。
こういったニーズがある中、少ない試料を効率的に回収するため、製品の表面に遺伝子・血液等のタンパク質が付着しにくい機能加工（二次加工）を施すことで回収効率を上げるという方法が採用されている。この方法として、例えば、プラスチック成形品の表面にフッ素やシリコーンを塗布する工法が挙げられる。また、これら機能材料をベースとなるプラスチック材料に練り込むことで表面を機能化する方法も提案されている（例えば、特許文献１～２参照。）。
However, with the advancement of analysis technology and culture technology, sophistication of products is required, and accurate analysis with a smaller number of samples is required for genes and blood, and uniform and stable analysis is performed for regenerative medicine and drug discovery. There is an increasing need for high-yield cell culture processes.
In response to these needs, in order to efficiently recover a small number of samples, there is a method to improve the recovery efficiency by performing functional processing (secondary processing) on the surface of the product to prevent proteins such as genes and blood from adhering. It has been adopted. Examples of this method include a method of applying fluorine or silicone to the surface of a plastic molded product. Further, a method of kneading these functional materials into a plastic material as a base to make the surface functional has also been proposed (see, for example, Patent Documents 1 and 2).
しかしながら、上記の方法は少量の試料を回収するという目的は果たしているが、不純物の溶出などの問題を解決しておらず、試料自体の純粋性を害する危険性を残している。
実際に再生医療の現場では、細胞培養における不純物の溶出の問題が報告されており、純粋かつ機能性を有した培養のためのプラスチック製品が求められている。また、同時に前述の機能を有したままコスト的には安価な製品であることが同時に求められ、今後の市場要求・拡大を見据えた上で早期に解決されるべき問題と捉えられている。
However, although the above method serves the purpose of recovering a small amount of sample, it does not solve problems such as elution of impurities and leaves a risk of impairing the purity of the sample itself.
In fact, in the field of regenerative medicine, the problem of elution of impurities in cell culture has been reported, and a pure and functional plastic product for culture is required. At the same time, it is required to be an inexpensive product in terms of cost while maintaining the above-mentioned functions, and it is regarded as a problem that should be solved as soon as possible in anticipation of future market demands and expansion.
本発明は、上記問題を解決するためになされたものであり、シリコーンとプラスチック高分子の無機・有機ハイブリッド構造を有するシロキサン共重合樹脂添加剤を使用し、少ない添加量で必要な機能性を発現するバイオテクノロジ分野で用いられるプラスチック成形品及びその製造方法を提供することを目的とする。 The present invention has been made to solve the above problems, and uses a siloxane copolymer resin additive having an inorganic / organic hybrid structure of silicone and a plastic polymer to exhibit the required functionality with a small amount of addition. It is an object of the present invention to provide a plastic molded product used in the field of biotechnology and a method for producing the same.
本発明は、上記課題を解決するため、以下の工法を採用する。
本発明は既に公知であるシロキサン共重合樹脂の特性を最大限に引き出すための加工プロセス、特に、射出成形法や押出成形法に係るものであって、使用する熱可塑性プラスチック（ＰＰ、ＰＣ、ＰＭＭＡ、ＣＯＰ、ＣＯＣ等）の成形条件が、機能性発現の重要なパラメータになることを見出した。
In the present invention, the following construction method is adopted in order to solve the above problems.
The present invention relates to a processing process for maximizing the characteristics of a siloxane copolymer resin already known, particularly an injection molding method or an extrusion molding method, and the thermoplastic plastic (PP, PC, PMMA) to be used is used. , COP, COC, etc.) was found to be an important parameter for functional expression.
そして、本発明は、熱可塑性プラスチックをベース材料とし、該熱可塑性プラスチックにシロキサン共重合樹脂を添加、混合したプラスチック材料を用いて成形された成形品からなるバイオテクノロジ分野で用いられるプラスチック成形品であって、前記成形品の「表面のＸＰＳ分析によるシロキサン成分の元素比率（ｗｔ％）」／「内部のＸＰＳ分析によるシロキサン成分の元素比率（ｗｔ％）」が、７以上であることを特徴とするものである。 The present invention is a plastic molded product used in the biotechnology field, which comprises a molded product obtained by using a thermoplastic material as a base material, adding a siloxane copolymer resin to the thermoplastic plastic, and mixing the mixture. Therefore, the "elemental ratio of siloxane component by surface XPS analysis (wt%)" / "elemental ratio of siloxane component by internal XPS analysis (wt%)" of the molded product is 7 or more. It is something to do.
また、本発明は、プラスチックをベース材料とし、該熱可塑性プラスチックにシロキサン共重合樹脂を添加、混合したプラスチック材料を用いるバイオテクノロジ分野で用いられるプラスチック成形品の製造方法であって、成形条件の冷却時間を２０秒以下に、金型温度を一般成形条件の温度より２０℃以上高く、それぞれ設定するようにしたことを特徴とするものである。 Further, the present invention is a method for manufacturing a plastic molded product used in the biotechnology field, which uses a plastic as a base material, a siloxane copolymer resin is added to the thermoplastic, and a mixed plastic material is used. It is characterized in that the time is set to 20 seconds or less and the mold temperature is set to be 20 ° C. or more higher than the temperature of general molding conditions.
本発明により、プラスチック成形品の表面改質が実現できる。具体的には、プラスチック表面の撥水・撥油効果が向上し、シリコーン素材を塗布した場合と同等の機能が発現できる。従来はプラスチック表面にシリコーン素材を塗布することでシリコーン素材がもつ機能を発現させていたが、本発明では少量のシロキサン共重合樹脂をプラスチック素材にあらかじめ混練し、特殊な成形条件で加工することにより、シリコーン素材を後に塗布することなく撥水・撥油効果を発現させ、ＤＮＡやタンパク質が付着しにくい、バイオテクノロジ分野で用いられるプラスチック成形品及びその製造方法を提供することができる。 According to the present invention, surface modification of a plastic molded product can be realized. Specifically, the water- and oil-repellent effects of the plastic surface are improved, and the same functions as when the silicone material is applied can be exhibited. Conventionally, the function of the silicone material was expressed by applying the silicone material to the plastic surface, but in the present invention, a small amount of siloxane copolymer resin is kneaded in advance with the plastic material and processed under special molding conditions. It is possible to provide a plastic molded product used in the biotechnology field, which exhibits a water-repellent and oil-repellent effect without applying a silicone material later, and to which DNA and proteins do not easily adhere, and a method for producing the same.
以下、本発明のバイオテクノロジ分野で用いられるプラスチック成形品及びその製造方法の実施の形態について説明する。 Hereinafter, embodiments of a plastic molded product used in the biotechnology field of the present invention and a method for manufacturing the same will be described.
本発明で使用するシロキサン共重合樹脂は、シリコーンとプラスチック高分子の無機・有機ハイブリッド添加材で、無機素材と有機素材が化学的に重合しており、異種材同士の単なる混合物でないところが従来の機能添加材と異なるところである。すなわち、機能を有する無機部が有機高分子と化学重合しているため物理的に分離しにくく、成形加工後の溶出（不純物の発生）を回避することができる。
具体的には、このシロキサン共重合樹脂をベースとなる熱可塑性プラスチックに添加すると、シロキサン共重合樹脂内の有機高分子（プラスチック）部はベースとなるプラスチックと相溶性があるため非常に馴染みやすい。一方、無機（シロキサン）部は相溶性がないため反発しやすく、この材料が溶融状態にある場合、相溶部である有機高分子側がベースとなる熱可塑性プラスチックと結びつき、相溶性がない無機（シロキサン）部が表面部へ押しやられるという現象を起こす。
これにより、プラスチック成形品の表面において、無機（シロキサン）部分が表面に浮き出ることになる一方で有機高分子（プラスチック）部がベースとなるプラスチックと相溶しているので溶出することなく無機部の機能を発現させることができる。
本発明では、このシロキサン共重合樹脂の特性に注目し、高分子中の無機（シロキサン）部を最も表面に浮かび上がらせる成形条件（熱可塑性プラスチックの樹脂温度、保圧、冷却時間、金型温度等）の相関性を見出した。
また、シリコーン塗布製品と同様の表面機能をプラスチック成形品単体で実現させることができた。
The siloxane copolymer resin used in the present invention is an inorganic / organic hybrid additive of silicone and a plastic polymer, and the conventional function is that the inorganic material and the organic material are chemically polymerized and are not merely a mixture of different materials. It is different from the additive material. That is, since the inorganic portion having a function is chemically polymerized with the organic polymer, it is difficult to physically separate the inorganic portion, and elution (generation of impurities) after the molding process can be avoided.
Specifically, when this siloxane copolymer resin is added to the base thermoplastic, the organic polymer (plastic) portion in the siloxane copolymer resin is compatible with the base plastic and is very familiar. On the other hand, the inorganic (siloxane) part is incompatible and easily repels, and when this material is in a molten state, the organic polymer side, which is the compatible part, binds to the base thermoplastic and is incompatible. It causes a phenomenon that the siloxane) part is pushed to the surface part.
As a result, on the surface of the plastic molded product, the inorganic (siloxane) part emerges on the surface, while the organic polymer (plastic) part is compatible with the base plastic, so that the inorganic part does not elute. The function can be expressed.
In the present invention, paying attention to the characteristics of this siloxane copolymer resin, molding conditions (resin temperature, holding pressure, cooling time, mold temperature, etc. of thermoplastics) that make the inorganic (siloxane) part in the polymer stand out most on the surface, etc. ) Was found.
In addition, the same surface function as the silicone-coated product could be realized by the plastic molded product alone.
［射出成形法］
まず、熱可塑性プラスチック射出成形におけるシロキサン共重合樹脂のシロキサン部（無機部）を表面に析出させる最適条件を見出すため、熱可塑性プラスチックとしてポリプロピレン樹脂（ＰＰ）をベースに試験を実施した。
[Injection molding method]
First, in order to find the optimum conditions for precipitating the siloxane portion (inorganic portion) of the siloxane copolymer resin on the surface in thermoplastic injection molding, a test was conducted using polypropylene resin (PP) as the thermoplastic.
［一般的な成形条件］
試験には、５０ｍｍ角、厚さ１ｍｍの試験片を成形できる試験金型を使用した。
成形条件は、一般的なポリプロピレン樹脂の条件を基準とし、樹脂温度、保圧、冷却時間、金型温度の条件を振ることで表面機能の変化を確認するようにした。表面機能は精製水と植物油による接触角を測定した。
使用する材料は、シロキサン共重合樹脂（三井化学ファイン社製、シロキサン共重合樹脂「イクスフォーラ」（登録商標））を使用し、ポリプロピレン樹脂への混練を行った。混練は二軸押出混練機（東芝機械社製）を用いて行った。混練においてシロキサン共重合樹脂とポリプロピレン樹脂の重量パーセントで、シロキサン共重合樹脂：３％＋ポリプロピレン樹脂：９７％〔３％含有材料〕、シロキサン共重合樹脂：５％＋ポリプロピレン樹脂：９５％〔５％含有材料〕、シロキサン共重合樹脂：１０％＋ポリプロピレン樹脂：９０％〔１０％含有材料〕の３種類を製作し、この材料を使用してパラメータでの機能検証をするため、射出成形機で成形を行った。初期成形条件は表１のとおりで、一般的な成形条件（本明細書において、「一般成形条件」という場合がある。）の下、シロキサン共重合樹脂の含有率（本明細書において、単に、「含有率」という場合がある。）を変えることによる表面機能（精製水の接触角）の測定した。
その測定結果を、表１及び図１に示す。
[General molding conditions]
For the test, a test mold capable of molding a 50 mm square and 1 mm thick test piece was used.
The molding conditions were based on the conditions of general polypropylene resin, and changes in surface function were confirmed by changing the conditions of resin temperature, holding pressure, cooling time, and mold temperature. For surface function, the contact angle between purified water and vegetable oil was measured.
As the material used, a siloxane copolymer resin (manufactured by Mitsui Kagaku Fine Co., Ltd., siloxane copolymer resin "IXFORA" (registered trademark)) was used and kneaded into a polypropylene resin. Kneading was performed using a twin-screw extrusion kneader (manufactured by Toshiba Machine Co., Ltd.). In kneading, by weight percent of siloxane copolymer resin and polypropylene resin, siloxane copolymer resin: 3% + polypropylene resin: 97% [material containing 3%], siloxane copolymer resin: 5% + polypropylene resin: 95% [5%] Containing material], siloxane copolymer resin: 10% + polypropylene resin: 90% [10% content material], and molded with an injection molding machine to verify the function with parameters using this material. Was done. The initial molding conditions are as shown in Table 1, and the content of the siloxane copolymer resin (in the present specification, simply referred to as “general molding conditions”) under general molding conditions (in the present specification, simply referred to as “general molding conditions”). The surface function (contact angle of purified water) was measured by changing the "content rate").
The measurement results are shown in Table 1 and FIG.
以上のように、一般的な成形条件においてシロキサン共重合樹脂の含有率を増やすことで成形品の撥水性が向上することが分かる。
この結果を基準とし、成形条件を変化させ、その成形条件での接触角を測定することで、表面機能の向上を図ることができる成形条件を見出すようにした。
As described above, it can be seen that the water repellency of the molded product is improved by increasing the content of the siloxane copolymer resin under general molding conditions.
Based on this result, we changed the molding conditions and measured the contact angle under the molding conditions to find the molding conditions that can improve the surface function.
［成形条件試験］
・樹脂温度
樹脂温度は、一般成形条件である１７０℃を基準に２２０℃まで１０℃きざみで成形を行った。
その測定結果（含有率１０％のデータ）を、図２及び図３に示す。
この結果から、樹脂温度が表面機能に与える影響は少ないと判断できる。
[Molding condition test]
-Resin temperature As for the resin temperature, molding was performed in 10 ° C increments up to 220 ° C based on the general molding condition of 170 ° C.
The measurement results (data with a content of 10%) are shown in FIGS. 2 and 3.
From this result, it can be judged that the resin temperature has little influence on the surface function.
・保圧
保圧は、一般成形条件である４０ＭＰａを基準に３０ＭＰａから１００ＭＰａまで成形を行った。
その測定結果（含有率１０％のデータ）を、図４及び図５に示す。
この結果から、精製水では保圧の変化はほとんどないが、植物油において保圧が高くなるほど撥油機能の低下がみられた。したがって、保圧については圧力が低い条件、具体的には、一般成形条件の保圧値を挟んで、－１０ＭＰａ～＋３０ＭＰａの範囲、好ましくは、－１０ＭＰａ～＋２０ＭＰａの範囲が表面機能の向上につながると判断できる。
-Holding pressure The holding pressure was formed from 30 MPa to 100 MPa based on the general molding condition of 40 MPa.
The measurement results (data with a content of 10%) are shown in FIGS. 4 and 5.
From this result, there was almost no change in the holding pressure in purified water, but the oil-repellent function decreased as the holding pressure increased in the vegetable oil. Therefore, regarding the holding pressure, a range of -10 MPa to +30 MPa, preferably a range of -10 MPa to +20 MPa is connected to the improvement of the surface function under the condition that the pressure is low, specifically, the holding value of the general molding condition is sandwiched between them. Can be judged.
・冷却時間
冷却時間は、一般成形条件である３０ｓを基準に３ｓから６０ｓまで成形を行った。
その測定結果（含有率１０％のデータ）を、図６及び図７に示す。
この結果から、精製水、植物油共に冷却時間が長くなるほど機能の低下がみられた。したがって、冷却時間については冷却時間が短いほど、具体的には、一般成形条件の３０ｓより短い、２０ｓ以下、好ましくは、１２ｓ以下、より好ましくは、数秒（３ｓ）程度が表面機能の向上につながると判断できる。
-Cooling time The cooling time was 3s to 60s based on the general molding condition of 30s.
The measurement results (data with a content of 10%) are shown in FIGS. 6 and 7.
From this result, it was found that the function of both purified water and vegetable oil deteriorated as the cooling time became longer. Therefore, as for the cooling time, the shorter the cooling time, specifically, 20 s or less, preferably 12 s or less, more preferably several seconds (3 s), which is shorter than the general molding condition of 30 s, leads to improvement of the surface function. Can be judged.
・金型温度
金型温度は、一般成形条件である４０℃を基準に４０℃から１００℃まで成形を行った。
その測定結果（含有率１０％のデータ）を、図８及び図９に示す。
この結果から、精製水、植物油共に金型温度が高くなるほど機能の向上がみられた。したがって、金型温度については金型温度が高いほど、具体的には、一般成形条件の４０℃より高い、一般成形条件の金型温度に対して、＋２０℃以上（～＋６０ＭＰａ）、好ましくは、＋３０℃以上、より好ましくは、＋５０℃以上が表面機能の向上につながると判断できる。
-Mold temperature The mold temperature was 40 ° C to 100 ° C based on the general molding condition of 40 ° C.
The measurement results (data with a content of 10%) are shown in FIGS. 8 and 9.
From this result, the function of both purified water and vegetable oil improved as the mold temperature increased. Therefore, regarding the mold temperature, the higher the mold temperature is, specifically, + 20 ° C. or higher (~ + 60 MPa), preferably + 60 MPa, with respect to the mold temperature under the general molding conditions, which is higher than the mold temperature under the general molding conditions of 40 ° C. It can be determined that + 30 ° C. or higher, more preferably + 50 ° C. or higher, leads to improvement in surface function.
以上の試験の検証結果より、シロキサン共重合樹脂による撥水・撥油性の機能向上には一般に推奨されている成形条件を基準にすると、金型温度〔一般成形条件より高温に設定〕及び冷却時間〔一般成形条件より短く設定〕に加えて、保圧〔一般成形条件と同程度かより低く設定〕、樹脂温度〔一般条件とほぼ同等〕の順で設定し、各成形品の形状に合わせて成形条件を最適化するのが有効であることが分かる。
したがって、シロキサン共重合樹脂の高機能化製品加工において、一般的な成形条件で条件設定を行うのではなく、上記のパラメータを効果のある順番に設定することが望ましい。
Based on the verification results of the above tests, the mold temperature [set to a higher temperature than the general molding conditions] and the cooling time are based on the molding conditions generally recommended for improving the water and oil repellency functions of the siloxane copolymer resin. In addition to [set shorter than general molding conditions], hold pressure [set to be about the same as or lower than general molding conditions] and resin temperature [almost equivalent to general molding conditions], and set according to the shape of each molded product. It can be seen that it is effective to optimize the molding conditions.
Therefore, in the processing of high-performance products of siloxane copolymer resins, it is desirable to set the above parameters in the order of effectiveness, instead of setting the conditions under general molding conditions.
これらの機能上のデータを踏まえ、実際にシロキサン共重合樹脂の無機（シロキサン）部が成形品表面に存在していることを、Ｘ線光電子分光分析装置（ＸＰＳ：アルバック・ファイ社製）を用い、分子レベルでの表面状態を確認した試験の測定結果を表２及び図１０に、最適条件で成形した成形品の内部の構造をスパッタリングによる深さ解析を実施した試験の測定結果を図１１及び図１２に示す。
ここで、試験は、表面機能の向上に効果のある成形条件である金型温度について、４０℃から１００℃まで変化させて成形を行った。他の成形条件は、冷却時間：３ｓ、保圧：５０ＭＰａ、樹脂温度：１７０℃とした。
Based on these functional data, the fact that the inorganic (siloxane) part of the siloxane copolymer resin actually exists on the surface of the molded product was determined by using an X-ray photoelectron spectroscopy analyzer (XPS: manufactured by ULVAC-PHI, Inc.). Table 2 and FIG. 10 show the measurement results of the test confirming the surface condition at the molecular level, and FIGS. 11 and 11 and FIG. It is shown in FIG.
Here, in the test, molding was performed by changing the mold temperature, which is a molding condition effective for improving the surface function, from 40 ° C. to 100 ° C. Other molding conditions were cooling time: 3 s, holding pressure: 50 MPa, and resin temperature: 170 ° C.
この結果から、表面機能を向上させる最適成形条件に近づくほど、高分子中の無機（シロキサン）部が表面に浮かび上がらせることで、成形品の表面のＳｉ（ケイ素）及びＯ（酸素）原子の比率が上がり、多くのシロキサンが成形品の表面に存在していることが分かる。
ここで、シロキサンが成形品の表面に存在している指標として、成形品の「表面のＸＰＳ分析によるシロキサン成分（Ｓｉ２ｐ＋Ｏ１ｓ）の元素比率（ｗｔ％）」／「内部（成形品の表面から１０００ｎｍ～）のＸＰＳ分析によるシロキサン成分（Ｓｉ２ｐ＋Ｏ１ｓ）の元素比率（ｗｔ％）」を算出し、表２の「Ｓｉ２ｐ＋Ｏ１ｓ含有比」の欄に記載した（実施例で、７．１～１０．４。比較例で、６．３。）。
また、図１１及び図１２は、成形品の表面から深さ２０００ｎｍまでをスパッタリングで掘り込み、ＳｉとＯの元素比率を確認したものであるが、表面の３１．２％から６００ｎｍ掘り込んだだけでＳｉとＯの元素比率が３．５％にまで落ち込み、それ以降は元素比率３％程度で落ち着いている。このことから、成形品の内部において、シロキサンは一様に分散して存在しているが、本発明による成形工法によって成形品表面だけにシロキサンを著しく顕在化させることができること、成形品の内部のシロキサン元素比率と成形品表面のシロキサン元素表面比率では約１０倍の違いが生じることを確認した。
From this result, the closer to the optimum molding conditions for improving the surface function, the more the inorganic (siloxane) part in the polymer emerges on the surface, and the ratio of Si (silicon) and O (oxygen) atoms on the surface of the molded product It can be seen that a large amount of siloxane is present on the surface of the molded product.
Here, as an index that siloxane exists on the surface of the molded product, "elemental ratio (wt%) of siloxane component (Si2p + O1s) by XPS analysis of the surface" / "inside (1000 nm from the surface of the molded product)" The elemental ratio (wt%) of the siloxane component (Si2p + O1s) by XPS analysis of) was calculated and described in the column of "Si2p + O1s content ratio" in Table 2 (7.1 to 10.4 in the example. Comparative example. So, 6.3.).
Further, in FIGS. 11 and 12, the element ratio of Si and O was confirmed by digging from the surface of the molded product to a depth of 2000 nm by sputtering, but only 31.2% to 600 nm of the surface was dug. The elemental ratio of Si and O dropped to 3.5%, and after that, the elemental ratio was about 3%. From this, although the siloxane is uniformly dispersed inside the molded product, the siloxane can be remarkably exposed only on the surface of the molded product by the molding method according to the present invention. It was confirmed that there was a difference of about 10 times between the siloxane element ratio and the siloxane element surface ratio on the surface of the molded product.
次に、シロキサン共重合樹脂の含有率を３％及び５％に変化させた場合の試験の測定結果を表３に示す。
ここで、試験は、シロキサン共重合樹脂の含有率を３％及び５％に変化させた以外の他の成形条件は、表２の比較例及び実施例４に準拠した。
Next, Table 3 shows the measurement results of the test when the content of the siloxane copolymer resin was changed to 3% and 5%.
Here, in the test, the molding conditions other than changing the content of the siloxane copolymer resin to 3% and 5% were based on Comparative Examples and Example 4 in Table 2.
この結果から、シロキサン共重合樹脂の含有率を３％及び５％に変化させた場合も、含有率が１０％の場合と同様のことがいえることを確認した。 From this result, it was confirmed that the same thing can be said when the content of the siloxane copolymer resin is changed to 3% and 5% as in the case where the content is 10%.
［押出成形法］
ところで、上記の射出成形法と同様に、押出成形法においても本発明の方法は有効である。
このことを、シロキサン共重合樹脂の含有率５％のポリプロピレンを使用し、外径Φ２．５ｍｍ、内径Φ１．５ｍｍのチューブを押出成形した結果を、図１３に示す。
図１３において、左側のグラフは一般的な押出成形法によって、右側のグラフは本発明方法によって、それぞれチューブを製作し、製作したチューブの表面と内面をそれぞれＸＰＳによって元素比率を測定したものである。
一般的な押出成形法の場合、ＳｉＯの比率が表面側が１３．２４％に対し、内面側が３３．７１％と高いのは押出成形機によりチューブが成形された直後、チューブを冷却水によって冷却していることによる。この現象は、射出成形法において金型表面温度が高機能化の重要なパラメータであったのと同様に、押出成形法において、表面と内側のＳｉＯの比率の差は、押出成形の際の温度、すなわち、押し出されたチューブが冷却水の中を通るときに、表面側が直接冷却水に当たり冷却されるため、内面側よりもＳｉＯの比率が低くなる。
一方、本発明方法の場合、押し出されたチューブの冷却を大気圧化で空冷で実施することによって、ＳｉＯの比率が表面側が２９．９８％、内面側が４２．４９％と、一般的な押出成形法と比較して格段に比率が上がるという結果を得た。
したがって、押出成形チューブの場合、製品の冷却温度、冷却法を変えることで高機能化を実現でき、特に、チューブの場合、製品の特性上、チューブの内側に液体が流れるため、チューブの内面側の高機能化を図る際には、従来機能材を内面に塗布する工法やプラズマ等を応用した表面改質が行われているが、本発明方法であれば押し出されたチューブの冷却制御をすることで機能性を向上でき、低コストの製造法といえる。
[Extrusion molding method]
By the way, the method of the present invention is also effective in the extrusion molding method as in the above-mentioned injection molding method.
FIG. 13 shows the result of extrusion molding of a tube having an outer diameter of Φ2.5 mm and an inner diameter of Φ1.5 mm using polypropylene having a siloxane copolymer resin content of 5%.
In FIG. 13, the graph on the left side is a general extrusion molding method, and the graph on the right side is a tube manufactured by the method of the present invention, and the element ratios of the surface and the inner surface of the manufactured tube are measured by XPS, respectively. ..
In the case of a general extrusion molding method, the ratio of SiO is 13.24% on the front surface side and 33.71% on the inner surface side, which is high immediately after the tube is molded by the extrusion molding machine, and the tube is cooled by cooling water. It depends on what you are doing. This phenomenon is similar to the fact that the mold surface temperature was an important parameter for high functionality in the injection molding method, and in the extrusion molding method, the difference in the ratio of the SiO on the surface and the inside is the temperature during extrusion molding. That is, when the extruded tube passes through the cooling water, the surface side directly hits the cooling water and is cooled, so that the ratio of SiO is lower than that on the inner surface side.
On the other hand, in the case of the method of the present invention, by cooling the extruded tube by air cooling at atmospheric pressure, the ratio of SiO is 29.98% on the front surface side and 42.49% on the inner surface side, which is a general extrusion molding. The result was that the ratio increased significantly compared to the law.
Therefore, in the case of an extruded tube, high functionality can be achieved by changing the cooling temperature and cooling method of the product. In particular, in the case of a tube, the liquid flows inside the tube due to the characteristics of the product, so the inner surface side of the tube In order to improve the functionality of the tube, the conventional method of applying a functional material to the inner surface and surface modification using plasma etc. are performed, but with the method of the present invention, the cooling of the extruded tube is controlled. This can improve functionality and can be said to be a low-cost manufacturing method.
以上の工法上の成果を踏まえ、実際の遺伝子分析で使用されるシングルユース製品を射出成形法（成形条件は表２の実施例４に準拠した。）により製作し、その機能確認を実施した。
以下にその結果を示す。
Based on the above results of the construction method, a single-use product used in actual gene analysis was manufactured by an injection molding method (molding conditions conformed to Example 4 in Table 2), and its function was confirmed.
The results are shown below.
［ピペットチップ（ポリプロピレン樹脂製）］
遺伝子分析や培養において試薬を吸引する際に使用される２００μｌピペットチップ（ポリプロピレン製）について、既存商品とシロキサン共重合樹脂を使用した本発明における新規成形法で製作した製品との機能比較を実施した。
図１４－１～図１４－４に、「液切れ試験（ＢＳＡ：ウシ血清アルブミン３ｗｔ％、グリセリン３０ｗｔ％）」、「ＤＮＡ吸着性試験」及び「タンパク質吸着性試験」の結果を示す。
比較対象製品として、ノンコーティングのポリプロピレンによるピペットチップ２種類（Ａ社、Ｂ社）、コーティングによる高機能ピペットチップ２種類（Ｃ社：ＭＰＣポリマーコーティング、Ｄ社：シリコーンコーティング）を選定し、シロキサン共重合樹脂１０％含有のピペットチップと比較した。
[Pipette tip (made of polypropylene resin)]
We compared the functions of the 200 μl pipette tip (made of polypropylene) used for aspirating reagents in gene analysis and culture with the existing product and the product manufactured by the novel molding method in the present invention using a siloxane copolymer resin. ..
14-1 to 14-4 show the results of the "drainage test (BSA:
Two types of non-coated polypropylene pipette tips (Company A and Company B) and two types of coated high-performance pipette tips (Company C: MPC polymer coating, Company D: Silicone coating) were selected as products for comparison, and both siloxanes were selected. It was compared with a pipette tip containing 10% of a polymer resin.
［マイクロチューブ（ポリプロピレン樹脂製）］
同様に、マイクロチューブ（ポリプロピレン製）について、既存商品とシロキサン共重合樹脂を使用した本発明における新規成形法で製作した製品との機能比較を実施した。
図１５－１～図１５－４に、「液切れ試験（ＢＳＡ：ウシ血清アルブミン３ｗｔ％、グリセリン３０ｗｔ％）」、「ＤＮＡ吸着性試験」及び「タンパク質吸着性試験」の結果を示す。
[Microtube (made of polypropylene resin)]
Similarly, regarding the microtube (made of polypropylene), the functional comparison between the existing product and the product manufactured by the novel molding method in the present invention using the siloxane copolymer resin was carried out.
FIGS. 15-1 to 15-4 show the results of the "drainage test (BSA:
［培養ディッシュ（ポリプロピレン樹脂製）］
同様に、培養ディッシュ（ポリプロピレン製）について、既存商品とシロキサン共重合樹脂を使用した本発明における新規成形法で製作した製品との機能比較を実施した。
図１６－１～図１６－４に、「液切れ試験（ＢＳＡ：ウシ血清アルブミン３ｗｔ％、グリセリン３０ｗｔ％）」、「ＤＮＡ吸着性試験」及び「タンパク質吸着性試験」の結果を示す。
[Culture dish (made of polypropylene resin)]
Similarly, regarding the cultured dish (made of polypropylene), a functional comparison was carried out between the existing product and the product manufactured by the novel molding method in the present invention using the siloxane copolymer resin.
FIGS. 16-1 to 16-4 show the results of the "drainage test (BSA:
［培養ディッシュ（ポリカーボネート樹脂製）］
同様に、培養ディッシュ（ポリカーボネート製）について、既存商品とシロキサン共重合樹脂を使用した本発明における新規成形法で製作した製品との機能比較を実施した。
ここで、成形条件は表４の実施例に準拠した。
図１７－１～図１７－４に、「液切れ試験（ＢＳＡ：ウシ血清アルブミン３ｗｔ％、グリセリン３０ｗｔ％）」、「ＤＮＡ吸着性試験」及び「タンパク質吸着性試験」の結果を示す。
[Culture dish (made of polycarbonate resin)]
Similarly, regarding the culture dish (made of polycarbonate), a functional comparison was carried out between the existing product and the product manufactured by the novel molding method in the present invention using the siloxane copolymer resin.
Here, the molding conditions were based on the examples in Table 4.
FIGS. 17-1 to 17-4 show the results of the "drainage test (BSA:
いずれの成形品についても、液切れにおいてはシロキサン共重合樹脂による新工法の製品が最もよい結果を得た。ＤＮＡ及びタンパク質の吸着性においては、Ａ／Ｂ／Ｃ社の製品は製品表面への吸着による残存量が多い数値となったが、Ｄ社のシリコーンコーティング品とシロキサン共重合樹脂では残存量が少なく、効果が得られた。特にシロキサン共重合樹脂はＤ社と同等に近い数値を示したため、溶出の弊害がないコーティングなしでの高機能化を実現できていることを確認した。 For all the molded products, the products of the new construction method using the siloxane copolymer resin gave the best results in terms of liquid drainage. Regarding the adsorptivity of DNA and protein, the products of A / B / C had a large residual amount due to adsorption on the product surface, but the silicone-coated products of D and the siloxane copolymer resin had a small residual amount. , The effect was obtained. In particular, since the siloxane copolymer resin showed a value close to that of Company D, it was confirmed that high functionality could be realized without a coating that does not have the adverse effect of elution.
以上、本発明のバイオテクノロジ分野で用いられる成形品及びその製造方法について、その実施例に基づいて説明したが、本発明は上記実施例に記載した構成に限定されるものではなく、その趣旨を逸脱しない範囲において適宜その構成を変更することができるものである。 The molded article and the manufacturing method thereof used in the biotechnology field of the present invention have been described above based on the examples thereof, but the present invention is not limited to the configuration described in the above examples, and the gist thereof is described. The configuration can be changed as appropriate within a range that does not deviate.
本発明のバイオテクノロジ分野で用いられる成形品及びその製造方法は、シリコーンとプラスチック高分子の無機・有機ハイブリッド構造を有するシロキサン共重合樹脂添加剤を使用し、少ない添加量で必要な機能性を発現することから、撥水性、撥油性及びＤＮＡやタンパク質低付着性を備えることが要求されるバイオテクノロジ分野で用いられる成形品からなるプラスチック製品、例えば、細胞培養容器、シリンジ、ノズル、マイクロチューブ等の遺伝子分析（ＰＣＲ）、細胞培養等のバイオテクノロジ分野で用いられるプラスチック製品の製造に好適に適用でき、これらの成形品を、簡易に、かつ、低コストで製造することができる。 The molded product and its manufacturing method used in the biotechnology field of the present invention use a siloxane copolymer resin additive having an inorganic / organic hybrid structure of silicone and a plastic polymer, and exhibit the required functionality with a small amount of addition. Therefore, plastic products made of molded products used in the biotechnology field, which are required to have water repellency, oil repellency and low adherence to DNA and proteins, for example, cell culture containers, syringes, nozzles, microtubes and the like. It can be suitably applied to the production of plastic products used in the fields of biotechnology such as gene analysis (PCR) and cell culture, and these molded products can be produced easily and at low cost.
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| JP2020172725A Pending JP2022064159A (en) | 2020-10-13 | 2020-10-13 | Plastic molding used in biotechnology field and production thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014239675A (en) * | 2013-03-29 | 2014-12-25 | 大日本印刷株式会社 | Structure, micro passage device, and method for using structure |
| JP2015024548A (en) * | 2013-07-25 | 2015-02-05 | 大日本印刷株式会社 | Water-repellent film |
| JPWO2017073533A1 (en) * | 2015-10-26 | 2018-08-09 | コニカミノルタ株式会社 | Cell expansion method and cell expansion kit for observing rare cells |
| JPWO2017154641A1 (en) * | 2016-03-08 | 2018-11-15 | 三井化学株式会社 | Mouthpiece, sheet for manufacturing piece of mouthpiece, and method for manufacturing mouthpiece |
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2020
- 2020-10-13 JP JP2020172725A patent/JP2022064159A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014239675A (en) * | 2013-03-29 | 2014-12-25 | 大日本印刷株式会社 | Structure, micro passage device, and method for using structure |
| JP2015024548A (en) * | 2013-07-25 | 2015-02-05 | 大日本印刷株式会社 | Water-repellent film |
| JPWO2017073533A1 (en) * | 2015-10-26 | 2018-08-09 | コニカミノルタ株式会社 | Cell expansion method and cell expansion kit for observing rare cells |
| JPWO2017154641A1 (en) * | 2016-03-08 | 2018-11-15 | 三井化学株式会社 | Mouthpiece, sheet for manufacturing piece of mouthpiece, and method for manufacturing mouthpiece |
Non-Patent Citations (1)
| Title |
|---|
| ファインケミカル, vol. 49(8), JPN6023025653, 15 August 2020 (2020-08-15), pages 26 - 30, ISSN: 0005091797 * |
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