Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/98460
標題: 連續同軸流之水相—有機相液-液微萃取技術之開發
The development of the aqueous-organic liquid-liquid micro-extraction technology with continuous coaxial flow
作者: 張友隆
Yu-Lung Chang
關鍵字: 液-液萃取
針扎效應
連續同軸流
liquid-liquid extraction
pinning effect
continuous coaxial flow
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摘要: 近年來的生物工程技術蓬勃發展,在製藥業上被廣泛應用,從原料到加工成藥品,大致可以分為上游前處理、中游反應以及下游的純化,每個階段都包含了各種不同的生物加工技術,只要改變其中一個步驟,皆會影響產率,這也使得藥品在流程的開發上,需要花費相當龐大的資金以及時間,為了降低生產成本,將生物工程中常見的各類元件微型化的技術也應運而生。 產品最終的產量以及品質,主要受下游加工影響。為了因應反應過程當中產物的不同物性與化性,下游加工利用此差異將產品分離及純化。本研究中針對液-液萃取的微型化系統來作探討。現有的微型化液-液萃取系統中,有三種最為常見的技術:液珠生成、膜分離以及並流之液-液萃取系統。此三種技術的開發,在使用上有所限制。 為了克服上述三種技術的限制,本研究的目的在發展出可連續流動、適用操作範圍大、有穩定的水相-有機相接觸面積並且不需額外的液體分離裝置之系統,為了達到目的,研究中在裝置內加入螺旋線圈使水溶液因拉普拉斯壓力(Laplace pressure)僅流動於螺旋線圈當中與有機溶劑形成一穩定接觸面,並以連續同軸流的方式進行萃取;螺旋線圈為可調式,藉由拉伸或壓縮螺旋線圈改變線圈間距,讓裝置在不同流率的情況下皆可有穩定的液體接觸面積以完成萃取。本系統亦可改變接觸時間、pH值以及更換萃取劑來進行生物加工效率最佳化。 研究中水溶液相包含50 mM的-甲基芐胺(-methylbenzylamine, -MBA)以及苯乙酮(acetophenone, APH),有機溶劑相為正庚烷(n-heptane),以此來模擬苯乙酮生產流程中的純化作業。實驗中測試了在線圈間距從0.156到0.335 mm下適用的操作範圍,從實驗結果得知操作範圍涵蓋從0.5至7300 l/min,另外一相液體中也無液珠生成;在得知裝置的流率適用範圍後,也驗證了在不同設置下的裝置中之萃取效率。
In recent years, bioengineering technology has flourished and is widely used in the pharmaceutical industry. From raw materials to processed drugs, it can be roughly divided into upstream pretreatment, midstream reaction and downstream purification. Each stage contains various bioprocessing technology. As long as you change one parameter of the steps, it will affect the yield. It also makes the drug development in the process takes a lot of money and time. In order to reduce the production cost, the techniques for miniaturizing devices in bioengineering have also emerged. The final output and quality of the product are mainly affected by downstream processing. The downstream processing utilizes the different physical properties and chemical properties of the reactants in process to separate and purify the product. In this study, the miniaturization system for liquid-liquid extraction was discussed. Among the existing miniaturized liquid-liquid extraction systems, there are three of the most common techniques: droplet based liquid-liquid extraction, membrane based liquid-liquid and co-flow liquid-liquid extraction systems. The development of these three technologies is limited in their use. But these three technologies are limited in their use. In order to overcome the limitations of the above three technologies, the purpose of this study was to develop a system that can be continuously flowed, has a wide operating range, has a stable aqueous-organic phase contact area, and does not require an additional liquid separation device. To achieve the purpose, a helix wire is added into the device to make the aqueous solution flow only in the helix wire and form a stable contact surface with the organic solvent due to the Laplace pressure. The extraction is carried out by continuous coaxial flow; The pitches of the helix wire are adjustable by stretching or compressing the helix wire. To allow the device to have a stable liquid contact area at different flow rates to complete the extraction. The system also optimizes bioprocessing efficiency by changing contact time, pH, and changing extractant. In the study, the aqueous phase contained 50 mM of -methylbenzylamine (-MBA) and acetophenone (APH), and the organic solvent phase was n-heptane, which was used to simulate the purification operations in the acetophenone production process. In the experiment, the applicable operating range of helix wire pitches are from 0.156 to 0.335 mm was tested. From the experimental results, the operating range was from 0.5 to 7300 l/min, and no droplet was formed in the other phase liquid. After the flow rate is applied, the extraction efficiency in the device at different settings is also verified.
URI: http://hdl.handle.net/11455/98460
文章公開時間: 2021-08-31
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