具有良好人體與環境相容性的材料在現今的研究領域逐漸受到重視，其中，仿生型雙離子材料如phosphobetaine(PB)、sulfobetaine(SB) 和 carboxybetaine(CB)等結構被視為目前的效能最佳方案。雙離子結構之仿生概念取自細胞膜表面的磷脂質(PB)，其正負電結構可形成穩定水合層使表面具有超親水性。甜菜鹼carboxylbetaine與硫代甜菜鹼sulfobetaine具有類似的雙離子結構可具備超親水性以抵抗生物性黏附，相較於PB， SB與CB有低成本與易於製備的優點。本研究將以甜菜鹼系列的SB與CB為主軸，分別在三個章節中討論其高分子結構的製作方法、材料特性與抗生物黏附效能，並應用於表面塗層與生物感測器的範疇。
第一個部分研究具有熱塑性質的雙離子共聚物結構，此結構可具有良好的高溫容忍度，並可抵抗各類型的生物黏附。 在共聚物poly(vinylpyrolidone)-co-poly(sulfobetaine methacrylate) (poly(VP-co-SBMA))之中，藉由精確地調控VP與SBMA在高分子中的組成比例，可使材料同時兼具熱容忍度與抗沾黏效果。 我們在研究中探討poly(VP-co-SBMA)製作成的水膠以及其熱塑後的網狀結構，在抵抗一般性生物黏附如蛋白質、細胞、細菌的效果。 值得注意的是，poly(VP-co-SBMA)共聚網狀結構在經過200度的熱塑處理後，可以具有塑形效果，並且仍可維持良好的抗生物沾黏特性。然而，雙離子的PSBMA共聚結構具有好的生物惰性，卻在高溫熱塑處理後發現喪失了抗生物沾黏的效果。我們同時得到最佳化的結果是，poly(VP-co-SBMA) 的共聚網狀結構需要有PSBMA的組成鏈段在32mol%到61mol%之間時可有效減低蛋白質吸附、組織細胞以及細菌貼附，進而提升材料在人體血液中的相容性。 根據此部分的研究，poly(VP-co-SBMA)共聚物可在高溫塑形後保持良好的抗生物沾黏效果，因此具有可應用在醫療器材中的潛力，例如在本研究中所舉出在金屬人工支架的應用實例。
在第二個部分的研究中，一個新的共聚物結構與塗層技術被用來挑戰全面性的塗佈，並能具備抗生物沾黏的需求。 我們設計出具有雙離子與環氧基團的ploy(glycidyl methacrylate-co-sulfobetaine methacrylate) (poly(GMA-co-SBMA))，其可接枝在多樣性的材料基板表面包含陶瓷、金屬、塑膠等。Poly(GMA-co-SBMA)的表面接枝原理是基於目標表面上的氫氧基團與高分子上的環氧基所進行的鹼性催化開環反應。基由此特性，再結合最佳化後的紫外光臭氧處裡與三乙胺鹼性催化，poly(GMA-co-SBMA)可以全面性的接枝在各種類型的材料基板如矽晶圓、玻璃、鈦、不鏽鋼與聚乙烯上，並形成雙離子化的表面。 Poly(GMA-co-SBMA)的最佳組成是當PGMA/PSBMA的莫爾比例在0.23與分子量在25 kDa時可最有效的抵抗生物性吸附，蛋白質吸附量可減低超過90%，而血球細胞，組織細胞以及細菌貼附皆能有效降低。此研究開發的抗生物沾黏接枝法，可全面的在各類多樣性的基材形成雙離子界面，並有極大的潛力應用在醫療材料的塗佈中。
在醫療診斷用的表面型元件應用上，最重要的課題是要能在複雜介質如人體血液之中精準的偵測生物標定物。在第三部分中，新型製作雙離子水膠塗層的方法被用來解決此課題。Poly(carboxybetaine acrylamide) (pCBAA) 所製作成的CB水膠薄層是將CBAA單體與CB型交聯劑carboxybetaine diacrylamide(CBAAX)直接旋轉塗布在金與氧化矽基板的表面而得。CB水膠薄層的厚度可藉由改變交聯劑的濃度而精準的控制在15到150奈米之間，同時此薄層可具有長時穩定性。 表面電漿共振感測器被用來測定CB水膠薄層在未稀釋人體血清中的蛋白質吸附效果，當厚度大於20奈米時可達到超低吸附的效果(小於5ng/cm2)。 此外，CB水膠薄層可高效率的被抗體修飾，進而偵測特定的生物標定物且不喪失抗生物沾黏特性。此技術提供了一個快速有效的方法來製作具有抗生物沾黏的表面電漿共振生物感測晶片，同時此技術極具潛力可應用在各類的植入性醫療器材與醫用生物感測器之上。

Recently, it is imperative regarded of the materials with well-defined human and environmental compatibility. The biomimic zwitterionic materials such as phosphobetaine(PB)、sulfobetaine(SB) 和 carboxybetaine(CB) are considered as the most efficient solutions for this issue. The concept of zwitterionic structure was firstly developed from the phospholipid of cell membrane surface. The neutral charge with positive and negtive is capable to fomr a stable hydration layer on the surface thereby providing the ultra-hydrophilicity. Carboxylbetaine and sulfobetaine contain a similar zwitterionic structure which could reduce the bio-fouling due to its hydrophilic characteristic. Meanwhile, CB and SB have the advantages of low-cost and facile synthesis. In this study, we use SB and CB as the antifouling strategy and discuss their antifouling property of polymer and the application of surface coating and biosensor.
In the first section, we introduced a thermo-settable zwitterionic copolymer to design a high temperature tolerance biomaterial as a general antifouling polymer interface. The original synthetic fouling-resistant copolymer, poly(vinylpyrolidone)-co-poly(sulfobetaine methacrylate) (poly(VP-co-SBMA)), is both thermal-tolerant and fouling-resistant, and the antifouling stability of copolymer coated interfaces can be effectively controlled by regulating the VP/SBMA composition ratio. We studied poly(VP-co-SBMA) copolymer gels and networks with a focus on their general resistance to protein, cell, and bacterial bio-adhesion, as influenced by the thermo-setting process. Interestingly, we found that the shape of the poly(VP-co-SBMA) copolymer material can be set at a high annealing temperature of 200°C while maintaining good antifouling properties. However, while the zwitterionic PSBMA polymer gels were bio-inert as expected, control of the fouling resistance of the PSBMA polymer networks was lost in the high-temperature annealing process. A poly(VP-co-SBMA) copolymer network composed of PSBMA segments at 32 mol% showed reduced fibrinogen adsorption, tissue cell adhesion, and bacterial attachment, but a relatively higher PSBMA content of 61 mol% was required to optimize resistance to platelet adhesion and erythrocyte attachment to confer hemocompatibility to human blood. We suggest that poly(VP-co-SBMA) copolymers capable of retaining stable fouling resistance after high temperature shaping have a potential application as thermo-settable materials in a bio-inert interface for medical devices, such as the thermo-settable coating on a stainless steel blood-compatible metal stent investigated in this study.
The second section reported that most biomaterials have a lack of a simple, efficient and robust antifouling modification approach that limits their potential for biomedical applications. The challenge is to develop a universal surface grafting solution to meet the antifouling requirement. In this work, a new formulation of zwitterionic sulfobetaine-based copolymer, ploy(glycidyl methacrylate-co-sulfobetaine methacrylate) (poly(GMA-co-SBMA)), is designed as a chemical for grafting onto material and is introduced for the surface zwitterionization of versatile biomaterials, including ceramic, metal, and plastics. The grafting principle used to stabilize the poly(GMA-co-SBMA) on the target surfaces is based the base-induced ring opening reaction between epoxied and hydroxyl groups. A universal surface modification procedure was developed and performed from an optimized sequence of ultra-violet ozone pretreatment and trimethylamine-catalyzed zwitterionization on a selective case of versatile surfaces including silicon wafer, ceramic glass, titanium, steel, and polystyrene. The prepared poly(GMA-co-SBMA) with an optimum PGMA/PSBMA ratio of 0.23 and a molecular weight of 25 kDa exhibited the best resistance to fibrinogen adsorption with over 90% reduction as well as blood cell activation, tissue cell adhesion and bacterial attachment on the zwitterionic copolymer grafted surfaces. The developed antifouling grafting introduces a universal modification method to generate zwitterionic interfaces on versatile biomaterial substrates, providing great potential for application in medical device coating.
For surface-based diagnostic devices to achieve reliable biomarker detection in complex media such as blood, preventing nonspecific protein adsorption and having high loading of biorecognition elements are paramount. In the third section, a novel method to produce nonfouling zwitterionic hydrogel coatings was developed to achieve these goals. Poly(carboxybetaine acrylamide) (pCBAA) hydrogel thin films (CBHTFs) prepared with a carboxybetaine diacrylamide crosslinker (CBAAX) were coated on gold and silicon dioxide surfaces via a simple spin coating process. The thickness of CBHTFs could be precisely controlled between 15 and 150 nm by varying the crosslinker concentration, and the films demonstrated excellent long-term stability. Protein adsorption from undiluted human blood serum onto the CBHTFs was measured with surface plasmon resonance (SPR). Hydrogel thin films greater than 20 nm exhibited ultra-low fouling (<5 ng/cm2). In addition, the CBHTFs were capable of high antibody functionalization for specific biomarker detection without compromising their nonfouling performance. This strategy provides a facile method to modify SPR biosensor chips with an advanced nonfouling material, and can be potentially expanded to a variety of implantable medical devices and diagnostic biosensors.

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