玻璃-PDMS-PC复合式微流控脱水芯片的研制

发布时间：2018-05-11 02:01

本文选题：正电子发射断层显像 + 显像剂合成　；参考：《浙江大学》2014年硕士论文

【摘要】：显像剂是正电子发射断层显像(PET)与核医学的关键。用于PET显像剂生产的常规合成仪具有许多不足之处：仪器设备体积庞大,价格非常昂贵；每次合成得到的PET显像剂的剂量较多,导致反应速率和反应效率降低；纯化步骤非常复杂；反应耗时长,难以实现按时按需生产；难以进行功能扩展,每合成一种PET显像剂需要一组专用设备,制约了新显像剂的研发工作。在微流控芯片中进行PET显像剂的合成具有显著优势。第一,微流控反应合成系统可以操控非常小的反应体积,因此反应物的相对浓度高,反应速率快,从而可以大大降低底物的使用量,降低纯化的难度。其次,可以极大的缩短合成时间,真正实现按需生产。第三,能显著提高反应的放化产率。第四,反应体系小,降低防护成本,提高安全性。第五,反应芯片功能扩展性强,可以充分满足科研需要。这些特点为快速高效制备短半衰期的11C,13N,18F放射性PET显像剂化合物提供了一个新的实验平台,在生命科学和临床医学方面具有广阔的应用前景。因此,研究微流控条件下合成PET显像剂具有十分重要的意义。本论文第一章综述了近年来微流控芯片中合成PET显像剂的研究进展。着重介绍了微流控条件下合成最常用的显像剂2-氟-2-脱氧-D-葡萄糖([18F]FDG),将现有的合成系统分为“流动型”和“模块式”两大类,并比较了两类合成系统的优缺点。第二章,研发了一种复合式微流控脱水芯片,用于完成[18F]FDG合成过程中的脱水步骤。这个芯片由玻璃、PDMS、PC三种材质制得,采用不可逆封接方法分别制得玻璃-PDMS液路半芯片、PC-PDMS气路半芯片,然后依靠外力将两个半芯片可逆封接形成具有玻璃-PDMS... PDMS-PC结构的全芯片。用此芯片对纯水、乙腈与水混合溶液以及实际样品进行脱水实验研究,结果令人满意,可以用于后续[18F]FDG显像剂的合成。
[Abstract]:Imaging agent is the key of PET and nuclear medicine. The conventional synthesizer used in the production of PET imaging agent has many disadvantages: the volume of instrument and equipment is huge and the price is very expensive, the dosage of PET imaging agent is more than that of each synthesis, which results in the decrease of reaction rate and reaction efficiency. The purification process is very complex, the reaction time is long, it is difficult to achieve timely production on demand, and it is difficult to expand the function. Each synthesis of PET imaging agent requires a set of special equipment, which restricts the research and development of new imaging agent. The synthesis of PET imaging agent in microfluidic chip has significant advantages. First, the microfluidic reaction synthesis system can control the very small reaction volume, so the relative concentration of reactants is high and the reaction rate is fast, which can greatly reduce the use of substrate and reduce the difficulty of purification. Second, can greatly shorten the synthesis time, real production on demand. Third, the radiochemical yield of the reaction can be improved significantly. The fourth, the reaction system is small, reduces the protection cost, enhances the safety. Fifth, the reaction-chip has strong expansibility and can fully meet the needs of scientific research. These characteristics provide a new experimental platform for rapid and efficient preparation of 11CX ~ (13) N ~ (+) ~ (18) F radioactive PET imaging agent compounds with short half-life, and have a broad application prospect in life sciences and clinical medicine. Therefore, it is of great significance to study the synthesis of PET imaging agents under microfluidic conditions. In the first chapter of this thesis, the research progress of synthetic PET imaging agents in microfluidic chips is reviewed. The synthesis of the most commonly used imaging agent 2-fluoro-2-deoxy-Dglucose ([18F] FDGN) under microfluidic control is introduced in this paper. The existing synthesis systems are divided into "flow type" and "modular type", and the advantages and disadvantages of the two kinds of synthesis systems are compared. In chapter 2, a composite microfluidic dehydration chip is developed to complete the dehydration process of [18F] FDG. The chip is made of three kinds of glass PDMSPC. Glass PDMS liquid circuit half chip PC-PDMS gas circuit half chip is made by irreversible sealing method, and then the two half chips are capped by external force to form glass PDMSs. Full chip of PDMS-PC structure. The dehydration experiments of pure water, acetonitrile and water mixed solution and real samples were carried out with this chip. The results are satisfactory and can be used for the synthesis of [18F] FDG imaging agent.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914

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