研究開發以碳氟化物促進氣體交換之生物反應器;Development of Gas Exchange-Enhanced Bioreactor Using Fluorocarbon Materials

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題名:	研究開發以碳氟化物促進氣體交換之生物反應器;Development of Gas Exchange-Enhanced Bioreactor Using Fluorocarbon Materials
作者:	李宇翔
貢獻者:	生物醫學工程研究所
關鍵詞:	研究領域：醫學工程
日期:	2011-08-01
上傳時間:	2012-01-17 17:24:29 (UTC+8)
出版者:	行政院國家科學委員會
摘要:	計畫背景：如何提升培養基內氣體交換的效率一直以來都是細胞/組織培養技術研究開發的課題之一。優良的氣體交換率能提升所供應的氣體在培養液裡的溶解量並且加速排出因生物體代謝而產生的氣體，以增進細胞的生長。除此之外，將所提供的氣體作最大化的應用，可降低操作成本，提高產品的經濟價值。目前雖然可以精準控制特定氣體(例如：二氧化碳)在培養箱內的濃度，但是與培養液作氣體交換的效率，仍然受限於培養液材料本身的物理性質，造成現行養殖技術在氣體交換率與細胞生長密度兩項要求上不易兼得。為了克服此一問題，國立中央大學生醫工程所協同索瑪佩思生物科技公司提出利用碳氟化物優良的氣體吸附特性來建構增進氣體交換效率的生物反應器。基於系統實際測試上的方便性以及商業利益考量，本計畫使用植物細胞；小球藻(Chlorella)的生長來當作測試該反應器效能的標的細胞。藉由本計畫的執行，除了拓展碳氟化物應用的廣度及經濟效益，更期許能帶動國內相關生技產業的發展，創造更高的產業利益。計畫執行方法與特點：本計畫利用含氟界面活性劑(Fluorosurfactants)和含氟碳化物液體(Fluorocarbon liquids)優異的氣體吸附能力，分別設計二種不同的細胞生物反應器，並以小球藻為研究對象。設計上細胞培養液以溶解含氟界面活性劑或接觸含氟碳化物液體的方式將細胞與前述含氟物質置於同一個反應器中，並利用循環流動的方式將碳氟化物所吸附的氣體帶出培養系統外進行氣體交換(CO2  O2)，之後再流回系統以供應細胞生長所需的氣體。以此方式建構之細胞生長系統預期有以下好處： 1. 解決現有技術中氣體交換效率與細胞生長密度無法兼得的困境。 2. 此生物培養系統可被廣泛應用於其他動植物細胞/組織的生長。尤其針對對於某些氣體(例如：氧氣與二氧化碳)敏感的細胞種類，而有助於生物/醫學工程的研究發展。 3. 擴展碳氟化物的應用，增加其被大量使用機會進而降低其原物料的價格。如此受益整個產界鏈。 4. 使得供應與排放的氣體能被充分的吸收並帶回給細胞所利用，增加氣體供應的效能。計畫執行優勢：中央大學生物醫學工程研究所(計畫申請人)在生物工程與細胞生物的研究有長期的研究發展，並具備使用含氟碳化物液體在生物技術應用上的實際經驗。合作廠商(索瑪佩思生物科技公司)對於各項碳氟化物具備專業應用知識，並對於計畫所需的含氟界面活性劑，具備完整供應與產製能力(經濟部科技研究發展專案產品。SBIR #1Z980534)。因此該研究組合足以執行此產學合作計劃案。預定研究工作項目：此研究計畫的目標是建立可增進氣體交換的生物反應器，並以小球藻作為測試該系統的標的細胞。未來一年規劃進行之研究工作項目如下: (1) 系統設計和設定各項操作條件，並評估不同設計之操作方法和效果。 (2) 碳氟化物的生物相容性測試。 (3) 比較實驗組與對照組，評估該生物反應器之效能。 (4) 系統放大再現性測試與經濟效益評估。 Background: Enhancing gas exchange in the culture medium is one of the desirable goals for advancing cell/tissue culture technology. Ideal gas exchange can increase the dissolved amount of supplied gas in the culture medium, and quickly remove the gas generated from the cell metabolism, yielding high cell proliferation. Furthermore, maximizing the utilization of supplied gas can diminish cost and whereby dramatically increase the value of product. Although the gas concentration can be precisely controlled in an incubator (e.g., CO2), the amount of gas dissolved into culture medium is still limited due to physical properties of medium, resulting good effect of gas exchange and high density-cell growth can not be offered simultaneously by the current technology. To overcome this challenge, NCU/BME and Somapex Biotech Inc. propose to establish gas exchange-enhanced bioreactors using fluorinated materials as gas mediators. Through the implementation of this project, we can not only extend the applications and values of fluorinated products, but further prompt Taiwan biotechnological development and generate more benefits for the entire industry accordingly. Method and Features: Two cell culture bioreactors are designed by using either fluorosurfactants or fluorocarbon liquids as the gas mediators since they both have excellent capability of gas adsorption. We use chlorellas to assess the developed bioreactors in this study. The culture medium will either dissolve fluorosurfactants, or contact with fluorocarbon liquids to allow cells and fluorinated materials in the same system. The fluorinated substances with absorbed gas will be driven outside of culture chamber to process gas exchange, and provide refreshed gas tochlorellas after flowing back. There are several advantages by using the developed bioreactors: 1. Improve the efficiency of gas exchange in the culture medium without sacrificing cell growth density. 2. The developed bioreactor can be widely used for animal and plant tissue/cell culture; especially for O2 and CO2-sensitive cell types, which is very helpful for biological / biomedical research. 3. Extend the application opportunities of fluorinated materials that will dramatically reduce the raw material prices, and whereby benefit all relative industries. 4. Maximize the utilization of supplied gas since it can be effectively absorbed by fluorinated materials and carried to cells. Advantages: Graduate Institute of Biomedical Engineering in NCU has long research development in the fields of bioengineering & cell biology, and has hands-on experience of fluorocarbon liquids handling in biotechnology applications. The partner; Somapex Biotech Inc. is a well-established biotech company with strong professions in fluorinated materials especially on fluorosurfactants (SBIR #1Z980534). Hence this partnership is perfectly qualified to conduct this industry-academia collaboration program. Specific Aims：The aim of one-year project is to establish a gas exchange-enhanced bioreactor for cell cultivation. The efficacy of the bioreactor will be assessed using chlorellas as experimental objects. The following tasks will be performed orderly: (1) Bioreactor designs, parameters configuration, and evaluation of different approaches. (2) Biocompatibility test of selected fluorinated materials. (3) Evaluation of the developed bioreactors as compared with the control group. (4) Reproducibility tests in scale-up system, and assessment of the product values applied to industries. 研究期間：10006 ~ 10105
關聯:	財團法人國家實驗研究院科技政策研究與資訊中心
顯示於類別:	[生物醫學工程研究所 ] 研究計畫

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