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京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第22511号 / 農博第2415号 / 新制||農||1078(附属図書館) / 学位論文||R2||N5291(農学部図書室) / 京都大学大学院農学研究科応用生物科学専攻 / (主査)教授 松浦 健二, 教授 大門 高明, 教授 森 直樹 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(文学) / 甲第24333号 / 文博第907号 / 新制||文||727(附属図書館) / 京都大学大学院文学研究科行動文化学専攻 / (主査)教授 水野 一晴, 教授 米家 泰作, 准教授 小坂 康之 / 学位規則第4条第1項該当 / Doctor of Letters / Kyoto University / DGAM

京都大学 / 新制・課程博士 / 博士(理学) / 甲第25147号 / 理博第5054号 / 新制||理||1720(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 緒方 博之, 教授 望月 敦史, 教授 西山 朋子 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

生技產業的發展以及育成中心的經營一直是受到矚目的議題，台灣在生技產業的發展上，已投入相當多的資源，至今明確且優異的成果卻甚為稀少。而台灣的生技廠商以中小企業為主，中小企業正是育成中心主要的輔導對象，因此生技型育成中心的經營成功與否，對於生技產業的發展將造成一定程度的影響。 透過文獻回顧的整理，本研究歸納出一般型育成中心之經營成功關鍵因素六項，分別為育成中心的經營者、各種網絡關係的建立、育成中心的企業化經營、進駐廠商的篩選與畢業過程、與大學保持密切的關係以及育成中心提供的服務內容。而藉由觀察國際上經營成功的生技型育成中心，發展出四項生技型育成中心之經營成功關鍵因素，分別為與醫院保持合作關係、配合園區的設立發展育成業務、具有多種技術平台的合作夥伴以及育成中心的國際化。綜合以上的分析，本研究以十項關鍵因素為基礎，透過個案訪談的方式，深入了解台灣生技型育成中心的現況，檢視以特定發展方向為主的育成中心，其發展狀況、營運方式以及成功之道，與一般育成中心的異同或特殊之處為何。 研究結果顯示，「技術」是台灣生技型育成中心在經營上最重要的關鍵，而與母組織互動越密切的育成中心成效亦較好。在一般型育成中心的六項經營關鍵成功因素上，各種網絡關係的建立 (例如對外部網絡的發展較不活絡、建立名聲)、企業化經營 (例如持續經營之資金與模式)、進駐廠商的篩選與畢業過程 (例如招商不易) 與育成中心提供的服務內容 (例如欠缺市場行銷與資金方面的能量) 等四項，對於育成中心的經營影響較大。在生技型育成中心的四個經營關鍵成功因素方面，與醫院保持合作關係為非必要之條件; 配合園區的設立發展育成業務與育成中心的國際化上，皆未有明確的規劃或明顯的表現; 對於具有多種技術平台的合作夥伴，目前在育成領域內並無實質的合作與整合效益出現，而以非正式的聯結關係為主，多數也認為轉變成正式的聯盟平台在執行上尚有許多困難待克服。 最後，本研究將生技型育成中心的發展程度，與該發展時期所需的關鍵成功因素做關聯，整體來說，台灣的生技型育成中心都還處於發展初期至中期。而參考國外發展歷程較久的生技型育成中心歸納得到的關鍵成功因素，對於台灣的生技型育成中心來說，是較遙遠的目標，就現階段而言，其經營成功因素大部分落在與一般型育成中心經營成功相同的關鍵上。 / Recent years, there were lots of attentions on the development of biotech industry and the operation of incubation center. Many resources have been invested in the biotech industry in Taiwan. However, superior or successful outcomes were rare. Moreover, most Taiwan biotech-related companies are small-medium enterprises which are the main coaching targets of incubation center. Therefore, the successful operation of incubation center would relate to and affect the development of biotech industry in Taiwan. Through reference review, six key success factors about general incubation center operation were identified as “the operator of incubation center”, “the establish of various relationship networks”, “operation by enterprise management”, “the selection of proper tenants and graduation exam for tenants”, “to keep close relationship with universities”, and “the incubation center’s service items”. In addition, by investigation of the successful foreign bio-incubation center, four key success factors which might influence the operation of bio-incubation center were concluded as “collaboration with hospitals”, “co-operation the development of bio-science parks and bio-incubation center”, “having partners with varieties of technologies”, and “the internationalization of incubation center”. Based on the ten factors above, this study would investigate the operation and development of bio-incubation center in Taiwan. In addition, the key success factors of general incubation centers would be compared with those of bio-incubation centers in order to give suggestions for success operation. According to the analysis, technology support is crucial and essential to the Taiwan bio-incubation center. In general, having better interaction with parent organization would result in better performance. Among the six key success factors of general incubation center, four of them influence the operation more deeply, which were “the establish of various relationship networks”, “operation by enterprise management”, “the selection of proper tenants and graduation exam for tenants”, “to keep close relationship with universities”, and “the incubation center’s service items”. For the four key success factors of bio-incubation center, “collaboration with hospitals” is not necessary; there were no obvious results or plan about the “co-operation the development of bio-science parks and bio-incubation center” and “the internationalization of incubation center”; “having partners with varieties of technologies” is focus on the informal collaboration. A formal technology platform based on alliance of incubation centers still faces many difficulties and most bio-incubation centers in Taiwan still considerate the possibility of this kind of collaborative platform. Finally, this study proposes a relation between bio-incubation center development stages and the key success factors. As a result, the developments of Taiwan bio-incubation centers are just in the beginning or middle stage. The four key success factors derived form foreign successful and well-developed bio-incubation centers might be a long-term goal to Taiwan bio-incubation centers.

生技產業的發展以及育成中心的經營一直是受到矚目的議題，台灣在生技產業的發展上，已投入相當多的資源，至今明確且優異的成果卻甚為稀少。育成中心在培育中小企業的類型中生技業一直是培育的重點之一，而生技產業涵蓋範圍極廣，從生物農業、動物疫苗、一直到醫藥、幹細胞療法等都屬於生技的範疇，且生技產業的法規限制高，那麼一家育成中心的資源與能力是否可以滿足不同類型產業的生技廠商？本文想要探討的是以育成中心的資源是否可以兼顧所有生技類型廠商的需求？並就藉由個案描述育成中心對進駐廠商的價值。 透過文獻回顧的整理，本研究歸納出一般型育成中心之經營成功關鍵因素六項。以台大創新育成中心與生技類進駐廠商為個案，介紹台大育成體系的架構與校方關係，再分別挑選飼料添加，技術服務，與傳統中草藥三個不同產業的進駐廠商，描述三個個案自其企業進駐育成中心發展至今，經營過程中所遭遇的狀況，與育成中心所提供的協助、資源。分析育成中心對廠商所提供的服務所產生的價值為何。 研究結果發現，同樣的育成中心服務，呈現於不同產業的進駐廠商，會有極大的差異，而不同的進駐廠商需要的育成中心所提供的服務要項也不盡相同，而台大育成中心內最有價值的部分來自於母組織台灣大學的學術資源，藉由豐沛、完整的各院所資源，台大創新育成中心才有可能滿足各個不同產業別的生技產業，但仍偏向技術上的升級與開發，對於資金融通、產品行銷等服務仍較無法滿足進駐廠商的需求。 關鍵字: 「生物技術」、「育成中心」、「關鍵成功因素」 / The development of the biotechnology industry and the management of the innovation incubation centers (IICs) have been topics that receive great attention. Taiwan has invested many resources in the development of the biotechnology industry. However, there has been no clear and outstanding result so far. Among all types of small business, IICs have been focusing on incubating biotechnology related industry. The biotechnology related industry broadly covers many fields such as bio-agriculture, animal vaccines, drugs and stem cell treatment. In addition, the regulation in biotechnology related industry is very strict. This article would like to discuss whether it is possible to use the resources of IICs to meet the need of all biotechnology companies in different fields. With the case study, this article would also describe the value of IICs to biotechnology companies which engage NTUIIC services. Through organizing the published articles, this study concludes that the key factors of managing successful regular-sized IICs are the six items listed below. Take National Taiwan University Innovation Incubation Center (NTUIIC) and the biotechnology companies that engage its services for example, he study introduced the structure of the incubation system in National Taiwan University (NTU) and the relationship between NTUIIC and NTU, and focused respectively on three fields: feeding, skill service and traditional Chinese herbal medicine. This article describes three cases from the time these three biotechnology companies engaged NTUIIC services until now, the challenges these companies faced in management process, and the supports and resources provided by NTUIIC, to analyze the value of the services provided by NTUIIC to these companies. The study results show that same IICs services provided to biotechnology companies in different fields will have enormously different impact; and different biotechnology companies need different services from IICs. The most valuable asset of NTUIIC is its academic resources. With abundant and complete resources each department in NTU has, NTUIIC can therefore satisfy the needs from biotechnology companies in many different fields. However, the service NTUIIC can provide is more related to the upgrades and development in the technology itself, not the financial or marketing services. Keywords: Biotechnology, Innovation Incubation Centers, Key Factors

1970年代第一個能夠特異性剪切DNA分子的限制酶問世，開啟了快速基因操作的年代，加上二十世紀後電腦以及資訊科技的飛躍發展，持續帶動生物科技產業的進步，因此二十世紀可以說是生物科技開始大幅躍進的重要時期。 　　在近二十年以來，中國大力發展生物科技產業，做為一個新興市場，在中國生物科技公司成長歷程將可做為其它生技公司發展的借鏡，因此本研究除了搜集、分析中國重要的人才引進、人才獎勵政策、企業經營獎勵政策外，還運用個案研究方法，深入探討基因測序起家的華大基因公司在每個時期發展之策略，分析出完整的公司發展策略，以做為其它生技公司發展的參考。 　　1999年時，在華大基因創業初期，一開始先以參加國際人類基因組計劃，向中國政府爭取啟動的科研資金，初期並不以盈利為目的，當時也沒有一個確切的獲利方式，先以爭取政府的支持為首要目標，再來以增加國際、國內的知名度為輔，等待著機會的到來。華大基因在初期也加大文章發表的力度，尤其是在世界頂級的幾大生物類期刋：Cell、Nature和Science上，目前也持續不斷的在這幾個頂級期刊上發表研究成果，初期也成功的打造華大基因為世界上一流的研究機構與企業。 　　在2010年初，華大利用從銀行拿到的六億人民幣的貸款，從Illumina購買了128台的新一代測序儀Hiseq2000。隨著這批新設備的到來，2012年測序數據產出的能力已經占了全球一半以上，因此華大被外界稱為測序工廠或是測序界的富士康。隨著華大基因測序能力及知名度的提升，一些科學家及科研單位開始尋求合作，這也是華大基因第一個商業模式的產生。 　　在2013年時，華大收購了美國的基因測序儀公司CG (Complete Genomics) ，補全其缺失的上游環節。同時，它也開始與眾多的機構展開密切的合作。從前，華大主要是針對科研、醫藥上的基因測序。從醫療、科研機構獲得的收入雖然比較穩定，但是其發展潛力遠不如針對大眾人群的基因服務。人群在生育、健康、基礎科研、複雜疾病等方面都可以應用到基因測序服務方面。而且，隨著精準醫療的興起，民眾對個性化醫療服務的需求也越來越旺盛。 　　經由「五力分析」和「技術採用生命週期」分析，可以了解到華大基因從科學研究開始，先建立公司的品牌知名度，再轉入科研測序服務及科研合作收費的方向，之後再併購上游供應商，再往下游的終端消費市場，打通了整個產業鏈，掌握了在整個產業中更多的主動權及話語權。華大基因的發展策略，也提供了將來許多生技公司在中國發展時的參考。 / Since the first restriction enzyme which specifically cuts DNA came out in 1970s, the era of rapid DNA manipulation began. In addition, the development of computer science and information technology in the 20th century drives the progress of biotechnology industries. Thus, the 20th century is a critical time period of biotechnology development. In the past two decades, China has been emphasizing biotechnology industries. The development progress of biotechnology companies in China, one of the major emerging market countries, should be an important target of related studies. In this study, the information of talent import and rewards and enterprise rewards in China are collected and analyzed. Furthermore, the strategies of every stage of BGI, a company initially conducted DNA sequencing, are investigated. The study reveals the comprehensive development strategy of BGI which shall be a reference for other biotechnology companies. In 1999, BGI started as an unprofitable organization and applied start-up capital from China government with a proposal to join the international human genome project. Instead of a clear profit model, BGI aimed for official supports and international visibility in the beginning, waiting for an opportunity to come. Since then, BGI has set up efforts to publish research papers especially in high impact journals such as Cell, Nature, and Science. After years, BGI has become a first-class research institute and enterprise. Early 2010, BGI got a bank loan of 600 million RMB and bought 128 new generation sequencers Hiseq2000 from Illumina. With this new equipment, DNA sequencing output of the company reached over half of global amounts. Hence, BGI was called “sequencing factory” or “Foxconn of the sequencing industry”. As BGI’s ability and reputation rises, scientists and research institutes started to set up collaborations with the company, thereby began the initial business model of BGI. In 2013, BGI acquired a DNA sequencing company Complete Genomics (CG) in United States to fill-up the upstream vendor part. At the same time, BGI also expanded its collaborations with more institutions. Though incomes from medical and research institutions are relatively stable, the potentials of genome sequencing serving the whole human population is far more large for the company. In addition, the identification and demand toward individualized precision medicine vastly grow as precision medicine is widely accepted. With Porter Five Forces Analysis and Technology Adoption Life Cycle analysis, the business model of BGI is proposed. In the beginning, the company established brand awareness through basic scientific researches. Then, BGI turned to provide DNA sequencing and scientific research services. Afterward, the company acquired upstream vendor. Finally, BGI develops end consumer market and successfully integrates the entire industry chain, getting initiative and discourse power in the biotechnology industry. The development strategy of BGI shall provide a reference for other biotechnology companies that are aiming to develop in China.

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在以添加純菌且濾料為蔗渣的生物濾床來處理含甲苯及乙酸乙酯混合廢氣時，發現菌株B5(Rhodococcus sp.)+菌株Ac6(Rhodococcus fascians)的組合具有加成性，可加快反應，其中菌株B5兼具分解甲苯及乙酸乙酯之分解能力，而菌株Ac6則只能分解乙酸乙酯。然而，為了實廠的應用，基於工程化的考量，本研究將改用一般性的泥炭土為濾料，並全面性檢討各種操作條件，以確認該方法之實用性。 由批次實驗結果得知，菌株B5＋菌株Ac6的組合最適生長之pH值在7.0左右，氮源則以氯化氨（NH4Cl）較佳，有添加緩衝溶液時菌株生長情形及去除率均較無添加緩衝溶液時好，乙酸乙酯降解之中間產物乙醇有共同溶解效應存在，其中氮源批次實驗的結果亦在生物濾床實際操作時得到驗證。 最後將菌株植入以泥炭土為濾料的生物濾床中，利用自動控制設備將進氣溼度維持在82﹪，濾床溫度維持在24∼28℃，並進流甲苯10ppm、乙酸乙酯100ppm（T/E=1/10）之混合廢氣，結果發現當濾料乾基含水率為4時，其甲苯和乙酸乙酯的去除效果最好，皆可完全被去除。 在生物濾床操作時比較純菌株B5和菌株B5+菌株Ac6兩種組合之去除效果，在相同條件下此兩組合的乙酸乙酯去除率皆可維持在100﹪，但在甲苯去除率方面，純菌株B5在甲苯去除率達最高點後又隨即下降，而菌株B5+菌株Ac6的組合甲苯去除率不但能達100﹪，同時去除率能維持穩定而無下降之問題，此結果亦在植種菌量加倍時得到驗證。 / 第一章 緒論 1 第二章 文獻回顧 3 2.1 甲苯及乙酸乙酯的特性 3 2.2 生物濾床的原理與現況 4 2.2.1 生物濾床廢氣處理機制 4 2.2.2 生物濾床相關的應用現況 5 2.3 生物濾床之操作因子 6 2.3.1 濾料的選擇 6 2.3.2 pH值 7 2.3.3 溫度 7 2.3.4 營養源 8 2.3.5 濾料含水率 9 2.4 生物濾床中甲苯及乙酸乙酯抑制機制之探討 10 2.4.1 甲苯的代謝途徑 10 2.4.2 乙酸乙酯的代謝途徑 10 2.4.3 適應限制（Adaptation limitation） 12 2.4.4 競爭性抑制（Competitive inhibition） 12 2.4.5 非競爭性抑制（Non-competitive inhibition） 13 2.4.6 反應產物抑制（Reaction product inhibition） 13 第三章 材料與方法 14 3.1 藥品及材料 14 3.2 批次試驗 15 3.2.1 初始酸鹼度的影響之批次試驗 15 3.2.2 氮源種類的影響之批次試驗 16 3.2.3 酸鹼度變化的影響之批次試驗 16 3.2.4 乙酸乙酯中間產物的影響之批次試驗 17 3.2.5 Ac6降解甲苯能力測試之批次實驗 18 3.3 生物濾床實驗 18 3.3.1 濾料的製備 18 3.3.2 生物濾床設備 18 3.3.3 操作條件 21 3.4 分析方法 21 3.4.1 濾料性質分析 21 3.4.2 有機氣體分析 22 3.4.3 光學密度O.D.600nm值 22 3.4.5 菌液之pH值 22 3.5 儀器設備 22 第四章 結果與討論 25 4.1 初始酸鹼度對去除率之影響 25 4.2 酸鹼度變化對去除率之影響 27 4.2.1 酸鹼度變化對菌株B5去除率之影響 28 4.2.2 酸鹼度變化對菌株Ac6去除率之影響 35 4.2.3 酸鹼度變化對菌株B5+菌株Ac6去除率之影響 41 4.3 氮源種類對去除率之影響 47 4.4 乙酸乙酯之中間產物-乙醇對去除率之影響 51 4.5 生物濾床濾料含水率對VOCs去除之影響 59 4.6 菌株植種量對生物濾床啟動之影響 63 4.7 菌株B5+菌株Ac6的組合對生物濾床之貢獻 66 4.8生物濾床之最大處理容量 69 第五章 結論與建議 73 5.1 結論 73 5.2 建議 74 國內外參考文獻 75