簡易檢索 / 詳目顯示

研究生: 曾顯權
Shian-chiuan Tzeng
論文名稱: 利用抗生物沾黏靜電紡絲應用於偵測大腸循環腫瘤細胞
Detection of Colon Cancer Circulating Tumor Cells with Anti-biofouling Electrospinning Fibers
指導教授: 陳建光
Jem-Kun Chen
口試委員: 楊銘乾
Ming-Chien Yang
李愛薇
none
學位類別: 碩士
Master
系所名稱: 工程學院 - 材料科學與工程系
Department of Materials Science and Engineering
論文出版年: 2014
畢業學年度: 102
語文別: 中文
論文頁數: 199
中文關鍵詞: 靜電紡絲、抗生物沾黏、循環腫瘤細胞、細胞抓取、上皮黏著分子、大腸癌臨床測試
外文關鍵詞: anti-EpCAM, cell capture, circulating tumor cell, antibiofouling, electrospinning, clinical trials of colon cancer
相關次數: 點閱:313下載:2
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

  本研究目的為設計一種複合奈米纖維偵測大腸癌病患外周血中的循環腫瘤細胞(CTCs),而CTCs偵測容易伴隨著許多白細胞的干擾。複合奈米纖維分別是由尼龍6 (Nylon-6)、聚丙烯酸 (Poly acrylic acid; PAA)與聚甲基丙烯酸磺基甜菜鹼 (Poly sulfobetaine methacrylate; PSBMA)所構成,其中Nylon-6是做為檢測基底材料,其用於防止奈米纖維水解於水中。PSBMA為抗生物沾黏材料,亦可以避免白血球沾附。PAA上的COOH官能基可以固定streptavidin與anti EpCAM biotin來進行CTCs的偵測。將此三種材料利用甲酸為溶劑依照不同比例混合,利用靜電紡絲製造出奈米纖維薄膜,以達到不水解、抗沾黏與富含anti EpCAM抗體的目的,Nylon-6/PSBMA/PAA的最佳混合比例為50/25/25。
  首先測試奈米纖維之抗生物沾黏能力,其發現具有高達84.8%抗血纖維蛋白原、82.4%抗內皮細胞與96.3%抗白細胞的抗沾黏能力。而進一步將三種大腸癌細胞株(DLD-1、HCT-116與HT-29)進行檢測,證實奈米纖維可從環境中僅有10至100顆的情況下來偵測CTCs,其結果為線性趨勢與高達65%的偵測效率。而在奈米纖維偵測外周血中的CTCs中,更發現了PSBMA的存在可以提高18.4%偵測能力。
  最後進行臨床實驗,偵測三位大腸癌患者(分別為第一期的女性、第二期的女性與第三期的女性),其每毫升血液中的CTCs數目個別為3.2、0與6.6。目前在血液中抓取CTC所面臨的阻礙,包含步驟繁雜與高成本,相對於複合奈米纖維的設計對於臨床上稀少的循環腫瘤細胞偵測是具備高度發展潛力的。


  In this study, we designed an electrospinning composite nanofiber to capture the colon circulating tumor cells (CTCs) from peripheral blood of colorn cancer patients. CTC detection always influences by extensive leukocyte contamination in human blood. We introduced nylon-6, poly acrylic acid (PAA) and poly sulfobetaine methacrylate (PSBMA) to electrospin as nanofibrous membranes. Nylon-6 is a substrate that can avoid the nanofibers to soluble in aqueous solution. PSBMA is a kind of anti-biofouling polymer to prevent leukocyte absorption. Carboxyl groups of PAA are the media to immobilizate antibody biotin labeling (anti-EpCAM biotin) for CTC capture. The results suggest that the nanofibers composition is optimized to obtain 50/25/25 for Nylon-6/PAA/PSBMA according to the results of antibiofouling and analyte properties.
  The nanofibers posses to 84.86%, 82.4% and 96.3% of antibiofouling property for fibrinogen, cell endothelial and leukocyte, respectively. Colon cancer cell line (DLD-1, HCT-116 and HT-29), 10 to 100 colon cancer cells, are exploited mixed in 0.4mL medium to perform the capture of CTCs. The results exhibit that detection efficiencies increase linearly upon ca. 65%. Antibiofouling property of PSBMA including is enhanced ca. 18.4% in peripheral blood for CTC detection. Finally, peripheral blood of three colon cancer patients (stage I, II and III) were exploited to examine the property of CTC capture using the naofibers in clinical test. The nanofibers could capture 3.2, 0 and 6.6 per ml of CTCs numbers from the three patients respectively in the clinical test. The current methodologies for CTC capture in peripheral blood always include multiple procedural steps with high cost. Therefore, the nanofiber can possess high potential to capture CTCs clinically.

摘要I ABSTRACTIII 誌謝V 目錄VII 表目錄XII 圖目錄XIII 1. 前言1 1.1. 研究背景1 1.2. 研究動機與目的3 2. 文獻回顧與理論4 2.1. 循環腫瘤細胞4 2.1.1. 循環腫瘤癌細胞介紹4 2.1.2. 循環腫瘤細胞收集之相關文獻7 2.2. 靜電紡絲發展20 2.2.1. 靜電紡絲原理21 2.2.2. 靜電紡絲裝置22 2.2.3. 影響靜電紡絲的參數25 2.3. 奈米粗糙表面應用於生物技術27 2.4. 聚醯胺-630 2.5. 聚丙烯酸34 2.6. 抗生物沾黏材料之簡介35 2.6.1. 雙離子性高分子(zwitterionic polymers)41 2.6.2. PC類雙離子性高分子42 2.6.3. SB類雙離子性高分子44 2.6.4. CB類雙離子性高分子45 2.7. 生物晶片表面分子固定法46 2.7.1. 共價鍵固定法(EDC-NHS reaction)48 2.7.2. 生物親和法(Streptavidin-biotein system)50 3. 儀器原理52 3.1. 三維光學輪廓儀52 3.2. X光光電能譜儀54 3.3. 高解析度場發射掃描式電子顯微鏡55 3.4. 螢光光譜儀57 3.5. 共軛焦顯微鏡58 4. 實驗流程與方法60 4.1. 實驗流程圖60 4.2. 實驗藥品61 4.3. 實驗儀器66 4.4. 實驗目的與步驟69 4.4.1. 聚合線性PSBMA69 4.4.2. 奈米纖維製備70 4.4.3. 掃描式電子顯微鏡試片製作73 4.4.4. 奈米纖維降解度74 4.4.5. 奈米纖維表面粗糙度75 4.4.6. 抗生物沾黏76 4.4.7. 奈米纖維表面改質81 4.4.8. 細胞培養、標記與染色87 4.4.9. 掃描式電子顯微鏡生物試片製作89 4.4.10. 血液樣品89 4.4.11. 奈米纖維抓取細胞89 5. 結果討論90 5.1. 奈米纖維特性分析90 5.1.1. 工作電壓與溶液流速90 5.1.2. 奈米纖維物理化學特性94 5.2. 奈米纖維抗生物沾黏特性111 5.2.1. 抗蛋白質沾黏111 5.2.2. 抗血管內皮細胞沾黏113 5.2.3. 抗白血球沾黏115 5.3. 奈米纖維表面改質分析117 5.3.1. 共價鍵固定法之表面改質117 5.3.2. 生物親合法之螢光分析122 5.4. 奈米纖維抓取循環腫瘤細胞123 5.4.1. 奈米纖維專一性抓取能力123 5.4.2. 抓取大腸癌細胞125 5.4.3. 模擬大腸癌病患血液128 5.4.3.1. 奈米纖維臨床模擬應用128 5.4.3.2. 抗沾黏高分子於臨床模擬之表現131 5.4.4. 大腸癌病患臨床實驗133 5.4.4.1. 細胞尺寸辨識133 5.4.4.2. 細胞角蛋白辨識135 5.4.4.3. 上皮細胞分子137 5.4.4.3.1. 臨床實驗139 6. 結論141 文獻回顧142 附錄174 授權書175

[1] Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA: a cancer journal for clinicians 2013;63:11-30.
[2] Fidler IJ. The pathogenesis of cancer metastasis: the'seed and soil'hypothesis revisited. Nature Reviews Cancer 2003;3:453-8.
[3] Braun S, Naume B. Circulating and disseminated tumor cells. Journal of clinical oncology 2005;23:1623-6.
[4] Pantel K, Muller V, Auer M, Nusser N, Harbeck N, Braun S. Detection and clinical implications of early systemic tumor cell dissemination in breast cancer. Clinical cancer research 2003;9:6326-34.
[5] Ashworth T. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J 1869;14:146-9.
[6] Evans R. The" seed and soil" hypothesis and the decline of radical surgery: a surgeon's opinion. Texas medicine 1990;86:85-9.
[7] Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. New England Journal of Medicine 2004;351:781-91.
[8] Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. Journal of Clinical Oncology 2008;26:3213-21.
[9] de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clinical Cancer Research 2008;14:6302-9.
[10] Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, et al. EMT and dissemination precede pancreatic tumor formation. Cell 2012;148:349-61.
[11] Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science 2011;331:1559-64.
[12] Schilling D, Todenhofer T, Hennenlotter J, Schwentner C, Fehm T, Stenzl A. Isolated, disseminated and circulating tumour cells in prostate cancer. Nature Reviews Urology 2012;9:448-63.
[13] Pavelic SK, Sedic M, Bosnjak H, Spaventi S, Pavelic K. Metastasis: new perspectives on an old problem. Mol Cancer 2011;10:10.1186.
[14] Bernards R, Weinberg RA. Metastasis genes: a progression puzzle. Nature 2002;418:823-.
[15] Pantel K, Brakenhoff RH. Dissecting the metastatic cascade. Nature Reviews Cancer 2004;4:448-56.
[16] Sawyers CL. The cancer biomarker problem. Nature 2008;452:548-52.
[17] Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer research 2006;66:8319-26.
[18] Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 2007;450:1235-9.
[19] Mostert B, Sleijfer S, Foekens JA, Gratama JW. Circulating tumor cells (CTCs): detection methods and their clinical relevance in breast cancer. Cancer treatment reviews 2009;35:463-74.
[20] Yu M, Stott S, Toner M, Maheswaran S, Haber DA. Circulating tumor cells: approaches to isolation and characterization. The Journal of cell biology 2011;192:373-82.
[21] Torino F, Bonmassar E, Bonmassar L, De Vecchis L, Barnabei A, Zuppi C, et al. Circulating tumor cells in colorectal cancer patients. Cancer treatment reviews 2013;39:759-72.
[22] Parkinson DR, Dracopoli N, Petty BG, Compton C, Cristofanilli M, Deisseroth A, et al. Considerations in the development of circulating tumor cell technology for clinical use. J Transl Med 2012;10:138.
[23] Galanzha EI, Zharov VP. Circulating tumor cell detection and capture by photoacoustic flow cytometry in vivo and ex vivo. Cancers 2013;5:1691-738.
[24] Alix-Panabieres C, Pantel K. Circulating tumor cells: liquid biopsy of cancer. Clinical chemistry 2013;59:110-8.
[25] Sun W, Jia C, Huang T, Sheng W, Li G, Zhang H, et al. High-Performance Size-Based Microdevice for the Detection Of Circulating Tumor Cells from Peripheral Blood in Rectal Cancer Patients. PloS one 2013;8:e75865.
[26] Lianidou ES, Markou A. Circulating tumor cells in breast cancer: detection systems, molecular characterization, and future challenges. Clinical chemistry 2011;57:1242-55.
[27] Rood KD, Bhattacharyya K, DeSouza T, Sengupta S, Gupta SK, Mosley JD, et al. Capture of circulating tumor cells using photoacoustic flowmetry and two phase flow. Journal of biomedical optics 2012;17:0612211-9.
[28] Fabbri F, Carloni S, Zoli W, Ulivi P, Gallerani G, Fici P, et al. Detection and recovery of circulating colon cancer cells using a dielectrophoresis-based device:KRAS mutation status in pure CTCs. Cancer letters 2013;335:225-31.
[29] Alix-Panabieres C, Schwarzenbach H, Pantel K. Circulating tumor cells and circulating tumor DNA. Annual review of medicine 2012;63:199-215.
[30] Went PT, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G, et al. Frequent EpCam protein expression in human carcinomas. Human pathology 2004;35:122-8.
[31] Powell AA, Talasaz AH, Zhang H, Coram MA, Reddy A, Deng G, et al. Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PloS one 2012;7:e33788.
[32] CELLSEARCHR CTC Test.
[33] Stott SL, Hsu C-H, Tsukrov DI, Yu M, Miyamoto DT, Waltman BA, et al. Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proceedings of the National Academy of Sciences 2010;107:18392-7.
[34] Autebert J, Coudert B, Bidard F-C, Pierga J-Y, Descroix S, Malaquin L, et al. Fully Automates immunomagnetic Lab-on-chip for rare cancer cells sorting. Enumeration and in-situ analysis. Proc Micro Total Analysis Systems2012.
[35] Pecot CV, Bischoff FZ, Mayer JA, Wong KL, Pham T, Bottsford-Miller J, et al. A novel platform for detection of CK+ and CK− CTCs. Cancer discovery 2011;1:580-6.
[36] Munz M, Baeuerle PA, Gires O. The emerging role of EpCAM in cancer and stem cell signaling. Cancer research 2009;69:5627-9.
[37] Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene 2004;23:5748-58.
[38] O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2006;445:106-10.
[39] Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences 2003;100:3983-8.
[40] Stingl J, Eaves CJ, Zandieh I, Emerman JT. Characterization of bipotent mammary epithelial progenitor cells in normal adult human breast tissue. Breast cancer research and treatment 2001;67:93-109.
[41] Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao H-l, et al. Human hepatic stem cells from fetal and postnatal donors. The Journal of experimental medicine 2007;204:1973-87.
[42] Trzpis M, McLaughlin P, van Goor H, Brinker M, van Dam G, de Leij L, et al. Expression of EpCAM is up‐regulated during regeneration of renal epithelia. The Journal of pathology 2008;216:201-8.
[43] Fong D, Seeber A, Terracciano L, Kasal A, Mazzoleni G, Lehne F, et al. Expression of EpCAMMF and EpCAMMT variants in human carcinomas. Journal of clinical pathology 2014;67:408-14.
[44] Kirfel J, Magin T, Reichelt J. Keratins: a structural scaffold with emerging functions. Cellular and Molecular Life Sciences CMLS 2003;60:56-71.
[45] Osborn M, Weber K. Intermediate filaments: cell-type-specific markers in differentiation and pathology. Cell 1982;31:303-6.
[46] Fuchs E, Weber K. Intermediate filaments: structure, dynamics, function and disease. Annual review of biochemistry 1994;63:345-82.
[47] Barak V, Goike H, Panaretakis KW, Einarsson R. Clinical utility of cytokeratins as tumor markers. Clinical biochemistry 2004;37:529-40.
[48] Gion M, Boracchi P, Dittadi R, Biganzoli E, Peloso L, Gatti C, et al. Quantitative measurement of soluble cytokeratin fragments in tissue cytosol of 599 node negative breast cancer patients: a prognostic marker possibly associated with apoptosis. Breast cancer research and treatment 2000;59:211-21.
[49] Sjostrom HA, H. Joensuu, U.-H. Stenman, J. Lundin, C. Blomqvist, J. Serum tumour markers CA 15-3, TPA, TPS, hCG β and TATI in the monitoring of chemotherapy response in metastatic breast cancer. Scandinavian journal of clinical & laboratory investigation 2001;61:431-41.
[50] Plebani M, Basso D, Navaglia F, De Paoli M, Tommasini A, Cipriani A. Clinical evaluation of seven tumour markers in lung cancer diagnosis: can any combination improve the results? British journal of cancer 1995;72:170-3.
[51] Bennink R, Van Poppel H, Billen J, Decoster M, Baert L, Mortelmans L, et al. Serum tissue polypeptide antigen (TPA): monoclonal or polyclonal radio-immunometric assay for the follow-up of bladder cancer. Anticancer research 1999;19:2609-14.
[52] Nicolini A, Caciagli M, Zampieri F, Ciampalini G, Carpi A, Spisni R, et al. Usefulness of CEA, TPA, GICA, CA 72.4, and CA 195 in the Diagnosis of primary colorectal cancer and at its relapse. Cancer detection and prevention 1994;19:183-95.
[53] Rosati G, Riccardi F, Tucci A. Use of tumor markers in the management of head and neck cancer. The International journal of biological markers 1999;15:179-83.
[54] Bustin S, Gyselman V, Williams N, Dorudi S. Detection of cytokeratins 19/20 and guanylyl cyclase C in peripheral blood of colorectal cancer patients. British Journal of Cancer 1999;79:1813.
[55] Alix-Panabieres C, Vendrell J-P, Slijper M, Pelle O, Barbotte E, Mercier G, et al. Full-length cytokeratin-19 is released by human tumor cells: a potential role in metastatic progression of breast cancer. Breast cancer research : BCR 2009;11:R39.
[56] Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature 2006;445:111-5.
[57] US patent 1975504 A ,Process and apparatus for preparing artificial threads.
[58] Reneker DH, Chun I. Nanometre diameter fibres of polymer, produced by electrospinning. Nanotechnology 1996;7:216.
[59] Huang Z-M, Zhang Y-Z, Kotaki M, Ramakrishna S. A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Composites science and technology 2003;63:2223-53.
[60] Guangming G, Juntao W, Lei J. Novel Polyimide Materials Produced by Electrospinning. Progress in Chemistry 2011;23:750-9.
[61] Xie J, Xia Y. Electrospinning: an enabling technique for nanostructured materials. Material Matters: 3-D Nano and Micro Structures 2008;3:19-22.
[62] Ziabari M, Mottaghitalab V, Haghi A. Application of direct tracking method for measuring electrospun nanofiber diameter. Brazilian Journal of Chemical Engineering 2009;26:53-62.
[63] Li F, Zhao Y, Song Y. Core-Shell nanofibers: Nano channel and capsule by coaxial electrospinning. 2010.
[64] Li J, Connell S, Shi R. Biomimetic architectures for tissue engineering. 2010.
[65] Tan S, Inai R, Kotaki M, Ramakrishna S. Systematic parameter study for ultra-fine fiber fabrication via electrospinning process. Polymer 2005;46:6128-34.
[66] Koski A, Yim K, Shivkumar S. Effect of molecular weight on fibrous PVA produced by electrospinning. Materials Letters 2004;58:493-7.
[67] Sihn S, Kim RY, Huh W, Lee K-H, Roy AK. Improvement of damage resistance in laminated composites with electrospun nano-interlayers. Composites Science and Technology 2008;68:673-83.
[68] Zhang C, Yuan X, Wu L, Han Y, Sheng J. Study on morphology of electrospun poly (vinyl alcohol) mats. European Polymer Journal 2005;41:423-32.
[69] Biggs MJ, Richards RG, Gadegaard N, McMurray RJ, Affrossman S, Wilkinson CD, et al. Interactions with nanoscale topography: adhesion quantification and signal transduction in cells of osteogenic and multipotent lineage. Journal of Biomedical Materials Research Part A 2009;91:195-208.
[70] Palin E, Liu H, Webster TJ. Mimicking the nanofeatures of bone increases bone-forming cell adhesion and proliferation. Nanotechnology 2005;16:1828.
[71] Dalby MJ, McCloy D, Robertson M, Wilkinson CD, Oreffo RO. Osteoprogenitor response to defined topographies with nanoscale depths. Biomaterials 2006;27:1306-15.
[72] Gittens RA, McLachlan T, Olivares-Navarrete R, Cai Y, Berner S, Tannenbaum R, et al. The effects of combined micron-/submicron-scale surface roughness and nanoscale features on cell proliferation and differentiation. Biomaterials 2011;32:3395-403.
[73] Tuttle iV PV, Rundell AE, Webster TJ. Influence of biologically inspired nanometer surface roughness on antigen–antibody interactions for immunoassay–biosensor applications. International journal of nanomedicine 2006;1:497.
[74] Han W, Allio BA, Foster DG, King MR. Nanoparticle coatings for enhanced capture of flowing cells in microtubes. ACS nano 2009;4:174-80.
[75] Washburn NR, Yamada KM, Simon Jr CG, Kennedy SB, Amis EJ. High-throughput investigation of osteoblast response to polymer crystallinity: influence of nanometer-scale roughness on proliferation. Biomaterials 2004;25:1215-24.
[76] Zhang H, Jia Z, Lv X, Zhou J, Chen L, Liu R, et al. Porous silicon optical microcavity biosensor on silicon-on-insulator wafer for sensitive DNA detection. Biosensors and Bioelectronics 2013;44:89-94.
[77] Munz M. Microstructure and roughness of photopolymerized poly (ethylene glycol) diacrylate hydrogel as measured by atomic force microscopy in amplitude and frequency modulation mode. Applied Surface Science 2013;279:300-9.
[78] Figueroa J, Magana S, Lim DV, Schlaf R. Characterization of fully functional spray-on antibody thin films. Applied Surface Science 2013.
[79] Klug J, Perez LA, Coronado EA, Lacconi GI. Chemical and electrochemical oxidation of silicon surfaces functionalized with APTES: the role of surface roughness in the AuNPs anchoring kinetics. The Journal of Physical Chemistry C 2013;117:11317-27.
[80] Stafiniak A, Boratyński B, Baranowska-Korczyc A, Szyszka A, Ramiączek-Krasowska M, Prażmowska J, et al. A novel electrospun ZnO nanofibers biosensor fabrication. Sensors and Actuators B: Chemical 2011;160:1413-8.
[81] Wang S, Wang H, Jiao J, Chen KJ, Owens GE, Kamei Ki, et al. Three‐Dimensional Nanostructured Substrates toward Efficient Capture of Circulating Tumor Cells. Angewandte Chemie 2009;121:9132-5.
[82] Pey J-L. Corrosion protection of pipes, fittings and component pieces of water treatment and pumping stations. Anti-Corrosion Methods and Materials 1997;44:94-9.
[83] Nirmala R, Nam KT, Park S-J, Shin Y-S, Navamathavan R, Kim HY. Formation of high aspect ratio polyamide-6 nanofibers via electrically induced double layer during electrospinning. Applied Surface Science 2010;256:6318-23.
[84] Aussawasathien D, Teerawattananon C, Vongachariya A. Separation of micron to sub-micron particles from water: electrospun nylon-6 nanofibrous membranes as pre-filters. Journal of Membrane Science 2008;315:11-9.
[85] Wang H, Li Y, Zuo Y, Li J, Ma S, Cheng L. Biocompatibility and osteogenesis of biomimetic nano-hydroxyapatite/polyamide composite scaffolds for bone tissue engineering. Biomaterials 2007;28:3338-48.
[86] Misra R, Chaudhari P. Osteoblasts response to nylon 6, 6 blended with single‐walled carbon nanohorn. Journal of Biomedical Materials Research Part A 2013;101:1059-68.
[87] Tan K, Obendorf SK. Fabrication and evaluation of electrospun nanofibrous antimicrobial nylon 6 membranes. Journal of Membrane Science 2007;305:287-98.
[88] Zhao H, Bau HH. On the effect of induced electro-osmosis on a cylindrical particle next to a surface. Langmuir 2007;23:4053-63.
[89] Green NG, Ramos A, Gonzalez A, Morgan H, Castellanos A. Fluid flow induced by nonuniform ac electric fields in electrolytes on microelectrodes. I. Experimental measurements. Physical review E 2000;61:4011.
[90] Green NG, Ramos A, Gonzalez A, Morgan H, Castellanos A. Fluid flow induced by nonuniform ac electric fields in electrolytes on microelectrodes. III. Observation of streamlines and numerical simulation. Physical review E 2002;66:026305.
[91] Gonzalez A, Ramos A, Green NG, Castellanos A, Morgan H. Fluid flow induced by nonuniform ac electric fields in electrolytes on microelectrodes. II. A linear double-layer analysis. Physical review E 2000;61:4019.
[92] Samperi F, Montaudo M, Puglisi C, Alicata R, Montaudo G. Essential role of chain ends in the Ny6/PBT exchange. A combined NMR and MALDI approach. Macromolecules 2003;36:7143-54.
[93] Schaefgen JR, Trivisonno CF. Polyelectrolyte Behavior of Polyamides. I. Viscosities of Solutions of Linear Polyamides in Formic Acid and in Sulfuric Acid1. Journal of the American Chemical Society 1951;73:4580-5.
[94] McGrath JE. Ring-Opening Polymerization. ACS Symposium Series 1985;286:1-22.
[95] Peppas NA, Hilt JZ, Khademhosseini A, Langer R. Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Advanced Materials 2006;18:1345-60.
[96] Sikes HD, Hansen RR, Johnson LM, Jenison R, Birks JW, Rowlen KL, et al. Using polymeric materials to generate an amplified response to molecular recognition events. Nature materials 2007;7:52-6.
[97] Krishnan S, Weinman CJ, Ober CK. Advances in polymers for anti-biofouling surfaces. Journal of Materials Chemistry 2008;18:3405-13.
[98] Georgiev GS, Kamenska EB, Vassileva ED, Kamenova IP, Georgieva VT, Iliev SB, et al. Self-assembly, antipolyelectrolyte effect, and nonbiofouling properties of polyzwitterions. Biomacromolecules 2006;7:1329-34.
[99] Singer SJ, Nicolson GL. The fluid mosaic model of the structure of cell membranes. Science 1972;175:720-31.
[100] Lewis AL. Phosphorylcholine-based polymers and their use in the prevention of biofouling. Colloids and Surfaces B: Biointerfaces 2000;18:261-75.
[101] Ishihara K, Nomura H, Mihara T, Kurita K, Iwasaki Y, Nakabayashi N. Why do phospholipid polymers reduce protein adsorption? Journal of biomedical materials research 1998;39:323-30.
[102] Zhao J, Shi Q, Luan S, Song L, Yang H, Shi H, et al. Improved biocompatibility and antifouling property of polypropylene non-woven fabric membrane by surface grafting zwitterionic polymer. Journal of Membrane Science 2011;369:5-12.
[103] Ishihara K, Ueda T, Nakabayashi N. Preparation of phospholipid polylners and their properties as polymer hydrogel membranes. Polymer Journal 1990;22:355-60.
[104] Ishihara K, Ziats NP, Tierney BP, Nakabayashi N, Anderson JM. Protein adsorption from human plasma is reduced on phospholipid polymers. Journal of biomedical materials research 1991;25:1397-407.
[105] Ishihara K, Oshida H, Endo Y, Ueda T, Watanabe A, Nakabayashi N. Hemocompatibility of human whole blood on polymers with a phospholipid polar group and its mechanism. Journal of biomedical materials research 1992;26:1543-52.
[106] Sugiyama K, Matsumoto T, Yamazaki Y. Evaluation of biocompatibility of the surface of polyethylene films modified with various water soluble polymers using Ar plasma‐post polymerization technique. Macromolecular Materials and Engineering 2000;282:5-12.
[107] Ishihara K, Iwasaki Y, Ebihara S, Shindo Y, Nakabayashi N. Photoinduced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on polyethylene membrane surface for obtaining blood cell adhesion resistance. Colloids and Surfaces B: Biointerfaces 2000;18:325-35.
[108] Xu Z-K, Dai Q-W, Wu J, Huang X-J, Yang Q. Covalent attachment of phospholipid analogous polymers to modify a polymeric membrane surface: a novel approach. Langmuir 2004;20:1481-8.
[109] Jiang S, Cao Z. Ultralow‐Fouling, Functionalizable, and Hydrolyzable Zwitterionic Materials and Their Derivatives for Biological Applications. Advanced Materials 2010;22:920-32.
[110] Zhang Z, Chao T, Chen S, Jiang S. Superlow fouling sulfobetaine and carboxybetaine polymers on glass slides. Langmuir 2006;22:10072-7.
[111] Shih Y-J, Chang Y. Tunable blood compatibility of polysulfobetaine from controllable molecular-weight dependence of zwitterionic nonfouling nature in aqueous solution. Langmuir 2010;26:17286-94.
[112] Zhang Z, Chen S, Chang Y, Jiang S. Surface grafted sulfobetaine polymers via atom transfer radical polymerization as superlow fouling coatings. The Journal of Physical Chemistry B 2006;110:10799-804.
[113] Ladd J, Zhang Z, Chen S, Hower JC, Jiang S. Zwitterionic polymers exhibiting high resistance to nonspecific protein adsorption from human serum and plasma. Biomacromolecules 2008;9:1357-61.
[114] Cheng G, Zhang Z, Chen S, Bryers JD, Jiang S. Inhibition of bacterial adhesion and biofilm formation on zwitterionic surfaces. Biomaterials 2007;28:4192-9.
[115] Zhang Z, Zhang M, Chen S, Horbett TA, Ratner BD, Jiang S. Blood compatibility of surfaces with superlow protein adsorption. Biomaterials 2008;29:4285-91.
[116] Zhang Z, Chao T, Liu L, Cheng G, Ratner BD, Jiang S. Zwitterionic hydrogels: an in vivo implantation study. Journal of Biomaterials Science, Polymer Edition 2009;20:1845-59.
[117] Chen S, Zheng J, Li L, Jiang S. Strong resistance of phosphorylcholine self-assembled monolayers to protein adsorption: insights into nonfouling properties of zwitterionic materials. Journal of the American Chemical Society 2005;127:14473-8.
[118] Vogler EA. Structure and reactivity of water at biomaterial surfaces. Advances in Colloid and Interface Science 1998;74:69-117.
[119] Vogler EA. Role of water in biomaterials. Biomaterials Science, 2nd edn(Elsevier Academic Press, San Diego, 2004) pp 2004;59.
[120] Zhao C, Li L, Wang Q, Yu Q, Zheng J. Effect of film thickness on the antifouling performance of poly (hydroxy-functional methacrylates) grafted surfaces. Langmuir 2011;27:4906-13.
[121] Holmlin RE, Chen X, Chapman RG, Takayama S, Whitesides GM. Zwitterionic SAMs that resist nonspecific adsorption of protein from aqueous buffer. Langmuir 2001;17:2841-50.
[122] Kudaibergenov S, Jaeger W, Laschewsky A. Polymeric betaines: synthesis, characterization, and application. Supramolecular Polymers Polymeric Betains Oligomers: Springer; 2006. p. 157-224.
[123] Chang Y, Chen S, Zhang Z, Jiang S. Highly protein-resistant coatings from well-defined diblock copolymers containing sulfobetaines. Langmuir 2006;22:2222-6.
[124] Cheng G, Xue H, Li G, Jiang S. Integrated antimicrobial and nonfouling hydrogels to inhibit the growth of planktonic bacterial cells and keep the surface clean. Langmuir 2010;26:10425-8.
[125] Carr LR, Zhou Y, Krause JE, Xue H, Jiang S. Uniform zwitterionic polymer hydrogels with a nonfouling and functionalizable crosslinker using photopolymerization. Biomaterials 2011;32:6893-9.
[126] Zhang Z, Chen S, Jiang S. Dual-functional biomimetic materials: nonfouling poly (carboxybetaine) with active functional groups for protein immobilization. Biomacromolecules 2006;7:3311-5.
[127] Keefe AJ, Brault ND, Jiang S. Suppressing surface reconstruction of superhydrophobic PDMS using a superhydrophilic zwitterionic polymer. Biomacromolecules 2012;13:1683-7.
[128] Ji Y, Wei Y, Liu X, Wang J, Ren K, Ji J. Zwitterionic polycarboxybetaine coating functionalized with REDV peptide to improve selectivity for endothelial cells. Journal of Biomedical Materials Research Part A 2012;100:1387-97.
[129] Rusmini F, Zhong Z, Feijen J. Protein immobilization strategies for protein biochips. Biomacromolecules 2007;8:1775-89.
[130] Hermanson GT. Bioconjugate techniques: Academic press; 2013.
[131] Sehgal D, Vijay IK. A method for the high efficiency of water-soluble carbodiimide-mediated amidation. Analytical biochemistry 1994;218:87-91.
[132] Zander NE, Orlicki JA, Rawlett AM, Beebe Jr TP. Quantification of Protein Incorporated into Electrospun Polycaprolactone Tissue Engineering Scaffolds. ACS applied materials & interfaces 2012;4:2074-81.
[133] Ye P, Xu Z-K, Wu J, Innocent C, Seta P. Nanofibrous membranes containing reactive groups: electrospinning from poly (acrylonitrile-co-maleic acid) for lipase immobilization. Macromolecules 2006;39:1041-5.
[134] ThermoScientific. NHS and Sulfo-NHS 2011.
[135] Weber PC, Ohlendorf D, Wendoloski J, Salemme F. Structural origins of high-affinity biotin binding to streptavidin. Science 1989;243:85-8.
[136] Smith CL, Milea JS, Nguyen GH. Immobilization of nucleic acids using biotin-strept (avidin) systems. Immobilisation of DNA on Chips II: Springer; 2005. p. 63-90.
[137] Bontempo D, Maynard HD. Streptavidin as a macroinitiator for polymerization: in situ protein-polymer conjugate formation. Journal of the American Chemical Society 2005;127:6508-9.
[138] Huang B-H, Lin Y, Zhang Z-L, Zhuan F, Liu A-A, Xie M, et al. Surface labeling of enveloped viruses assisted by host cells. ACS chemical biology 2012;7:683-8.
[139] Lehnert M, Gorbahn M, Rosin C, Klein M, Köper I, Al-Nawas B, et al. Adsorption and conformation behavior of biotinylated fibronectin on streptavidin-modified TiOX surfaces studied by SPR and AFM. Langmuir 2011;27:7743-51.
[140] Joo K-I, Lei Y, Lee C-L, Lo J, Xie J, Hamm-Alvarez SF, et al. Site-specific labeling of enveloped viruses with quantum dots for single virus tracking. ACS nano 2008;2:1553-62.
[141] Zhang Z, Chao T, Jiang S. Physical, chemical, and chemical-physical double network of zwitterionic hydrogels. The Journal of Physical Chemistry B 2008;112:5327-32.
[142] Wu L, Ding J. In vitro degradation of three-dimensional porous poly (D,L-lactide-co-glycolide) scaffolds for tissue engineering. Biomaterials 2004;25:5821-30.
[143] Kanehira K, Banzai T, Ogino C, Shimizu N, Kubota Y, Sonezaki S. Properties of TiO2–polyacrylic acid dispersions with potential for molecular recognition. Colloids and Surfaces B: Biointerfaces 2008;64:10-5.
[144] Gu H, Yang Z, Gao J, Chang C, Xu B. Heterodimers of nanoparticles: Formation at a liquid-liquid interface and particle-specific surface modification by functional molecules. Journal of the American Chemical Society 2005;127:34-5.
[145] Hašek J, Streiblova E. Fluorescence microscopy methods. Yeast Protocols: Springer; 1996. p. 391-405.
[146] Gazouli M, Lyberopoulou A, Pericleous P, Rizos S, Aravantinos G, Nikiteas N, et al. Development of a quantum-dot-labelled magnetic immunoassay method for circulating colorectal cancer cell detection. World journal of gastroenterology: WJG 2012;18:4419.
[147] Wu D, Feng F, Xie D, Chen Y, Tan W, Schanze KS. Helical Conjugated Polyelectrolyte Aggregation Induced by Biotin–Avidin Interaction. The Journal of Physical Chemistry Letters 2012;3:1711-5.
[148] Yuk JS, Trnavsky M, McDonagh C, MacCraith BD. Surface plasmon-coupled emission (SPCE)-based immunoassay using a novel paraboloid array biochip. Biosensors and Bioelectronics 2010;25:1344-9.
[149] Liaw L, Lindner V, Schwartz SM, Chambers AF, Giachelli CM. Osteopontin and β3 integrin are coordinately expressed in regenerating endothelium in vivo and stimulate Arg-Gly-Asp–dependent endothelial migration in vitro. Circulation research 1995;77:665-72.
[150] Nasouri K, Haji A, Shoushtari A, Kaflou A. A Novel Study of Electrospun Nanofibers Morphology as a Function of Polymer Solution Properties.
[151] Desai K, Kit K, Li J, Zivanovic S. Morphological and surface properties of electrospun chitosan nanofibers. Biomacromolecules 2008;9:1000-6.
[152] Park KE, Kang HK, Lee SJ, Min B-M, Park WH. Biomimetic nanofibrous scaffolds: preparation and characterization of PGA/chitin blend nanofibers. Biomacromolecules 2006;7:635-43.
[153] Ohkawa K, Minato K-I, Kumagai G, Hayashi S, Yamamoto H. Chitosan nanofiber. Biomacromolecules 2006;7:3291-4.
[154] Kim B, Park H, Lee S-H, Sigmund WM. Poly (acrylic acid) nanofibers by electrospinning. Materials letters 2005;59:829-32.
[155] Emerick E, Grant S, Bernards M. Electrospinning of Sulfobetaine Methacrylate Nanofibers. SciMedcentral 2013;1003.
[156] Xu C, Yang F, Wang S, Ramakrishna S. In vitro study of human vascular endothelial cell function on materials with various surface roughness. Journal of Biomedical Materials Research Part A 2004;71:154-61.
[157] Sekine J, Luo SC, Wang S, Zhu B, Tseng HR, Yu Hh. Functionalized conducting polymer nanodots for enhanced cell capturing: the synergistic effect of capture agents and nanostructures. Advanced Materials 2011;23:4788-92.
[158] Ren K, Ji J, Shen J. Construction and enzymatic degradation of multilayered poly-L-lysine/DNA films. Biomaterials 2006;27:1152-9.
[159] Sun JT, Yu ZQ, Hong CY, Pan CY. Biocompatible Zwitterionic Sulfobetaine Copolymer‐Coated Mesoporous Silica Nanoparticles for Temperature‐Responsive Drug Release. Macromolecular rapid communications 2012;33:811-8.
[160] Yun J, Im JS, Lee Y-S, Kim H-I. Electro-responsive transdermal drug delivery behavior of PVA/PAA/MWCNT nanofibers. European Polymer Journal 2011;47:1893-902.
[161] Lalani R, Liu L. Electrospun zwitterionic poly (sulfobetaine methacrylate) for nonadherent, superabsorbent, and antimicrobial wound dressing applications. Biomacromolecules 2012;13:1853-63.
[162] Choi H-S, Kim Y-S, Zhang Y, Tang S, Myung S-W, Shin B-C. Plasma-induced graft co-polymerization of acrylic acid onto the polyurethane surface. Surface and Coatings Technology 2004;182:55-64.
[163] Liu Q, Singh A, Liu L. Amino acid-based zwitterionic poly (serine methacrylate) as an antifouling material. Biomacromolecules 2012;14:226-31.
[164] Lampin M, Warocquier‐Clerout R, Legris C, Degrange M, Sigot‐Luizard M. Correlation between substratum roughness and wettability, cell adhesion, and cell migration. Journal of biomedical materials research 1997;36:99-108.
[165] Zhao Y-F, Zhu L-P, Yi Z, Zhu B-K, Xu Y-Y. Improving the hydrophilicity and fouling-resistance of polysulfone ultrafiltration membranes via surface zwitterionicalization mediated by polysulfone-based triblock copolymer additive. Journal of Membrane Science 2013;440:40-7.
[166] Kubes P, Kerfoot SM. Leukocyte recruitment in the microcirculation: the rolling paradigm revisited. Physiology 2001;16:76-80.
[167] Tyan Y-C, Liao J-D, Klauser R, Wu I-D, Weng C-C. Assessment and characterization of degradation effect for the varied degrees of ultra-violet radiation onto the collagen-bonded polypropylene non-woven fabric surfaces. Biomaterials 2002;23:65-76.
[168] Cole MA, Voelcker NH, Thissen H, Horn RG, Griesser HJ. Colloid probe AFM study of thermal collapse and protein interactions of poly (N-isopropylacrylamide) coatings. Soft Matter 2010;6:2657-67.
[169] Lee S-W, Takahara N, Korposh S, Yang D-H, Toko K, Kunitake T. Nanoassembled thin film gas sensors. III. Sensitive detection of amine odors using TiO2/poly (acrylic acid) ultrathin film quartz crystal microbalance sensors. Analytical chemistry 2010;82:2228-36.
[170] Dauphas S, Ababou-Girard S, Girard A, Le Bihan F, Mohammed-Brahim T, Vie V, et al. Stepwise functionalization of SiNX surfaces for covalent immobilization of antibodies. Thin Solid Films 2009;517:6016-22.
[171] Pegoretti A, Fambri L, Migliaresi C. Interfacial stress transfer in nylon‐6/E‐Glass microcomposites: Effect of temperature and strain rate. Polymer composites 2000;21:466-75.
[172] Amaral I, Granja P, Barbosa M. Chemical modification of chitosan by phosphorylation: an XPS, FT-IR and SEM study. Journal of Biomaterials Science, Polymer Edition 2005;16:1575-93.
[173] Galtayries A, Warocquier‐Clerout R, Nagel MD, Marcus P. Fibronectin adsorption on Fe–Cr alloy studied by XPS. Surface and interface analysis 2006;38:186-90.
[174] Kanwar SS, Yu Y, Nautiyal J, Patel BB, Majumdar AP. The Wnt/β-catenin pathway regulates growth and maintenance of colonospheres. Molecular cancer 2010;9:212.
[175] Chen J, Li J, Sun Y. Microfluidic approaches for cancer cell detection, characterization, and separation. Lab on a Chip 2012;12:1753-67.
[176] Chua K-N, Chai C, Lee P-C, Tang Y-N, Ramakrishna S, Leong KW, et al. Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells. Biomaterials 2006;27:6043-51.
[177] He C, Nie CX, Zhao WF, Ma L, Xiang T, Cheng CS, et al. Modification of polyethersulfone membranes using terpolymers engineered and integrated antifouling and anticoagulant properties. Polymers for Advanced Technologies 2013;24:1040-50.
[178] Chen W, Weng S, Zhang F, Allen S, Li X, Bao L, et al. Nanoroughened surfaces for efficient capture of circulating tumor cells without using capture antibodies. ACS nano 2012;7:566-75.
[179] Lee S-K, Kim G-S, Wu Y, Kim D-J, Lu Y, Kwak M, et al. Nanowire substrate-based laser scanning cytometry for quantitation of circulating tumor cells. Nano letters 2012;12:2697-704.
[180] Wang Y, Zhou F, Liu X, Yuan L, Li D, Wang Y, et al. Aptamer-Modified Micro/Nanostructured Surfaces: Efficient Capture of Ramos Cells in Serum Environment. ACS applied materials & interfaces 2013;5:3816-23.
[181] Khashan S, Alazzam A, Furlani E. Computational Analysis of Enhanced Magnetic Bioseparation in Microfluidic Systems with Flow-Invasive Magnetic Elements. Scientific Reports 2014;4.
[182] Zheng S, Liu J-Q, Tai Y-C. Streamline-based microfluidic devices for erythrocytes and leukocytes separation. Microelectromechanical Systems, Journal of 2008;17:1029-38.
[183] Gujral TS, MacBeath G. A system-wide investigation of the dynamics of Wnt signaling reveals novel phases of transcriptional regulation. PloS one 2010;5:e10024.
[184] Vermeulen L, Felipe De Sousa EM, van der Heijden M, Cameron K, de Jong JH, Borovski T, et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nature cell biology 2010;12:468-76.
[185] Patriarca C, Macchi RM, Marschner AK, Mellstedt H. Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer treatment reviews 2012;38:68-75.
[186] Went P, Vasei M, Bubendorf L, Terracciano L, Tornillo L, Riede U, et al. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. British journal of cancer 2006;94:128-35.
[187] Sukhdeo K, Paramban RI, Vidal JG, Elia J, Martin J, Rivera M, et al. Multiplex flow cytometry barcoding and antibody arrays identify surface antigen profiles of primary and metastatic colon cancer cell lines. PloS one 2013;8:e53015.
[188] Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clinical Cancer Research 2004;10:6897-904.
[189] Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH, Dive C. Molecular analysis of circulating tumour cells[mdash]biology and biomarkers. Nat Rev Clin Oncol 2014;11:129-44.
[190] Lu C, Tsai H, Uen Y, Hu H, Chen C, Cheng T, et al. Circulating tumor cells as a surrogate marker for determining clinical outcome to mFOLFOX chemotherapy in patients with stage III colon cancer. British journal of cancer 2013;108:791-7.
[191] Peach G, Kim C, Zacharakis E, Purkayastha S, Ziprin P. Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review. British journal of cancer 2010;102:1327-34.

無法下載圖示 全文公開日期 2019/07/30 (校內網路)
全文公開日期 本全文未授權公開 (校外網路)
全文公開日期 本全文未授權公開 (國家圖書館:臺灣博碩士論文系統)
QR CODE