基于微流控芯片的^18F微反应器的研制与应用

Manufacture and application of a microfluidic chip-based ^18F microreactor

目的研发一种基于微流控芯片技术的^18F微反应器，并将其用于合成^18F标记的放射性药物。方法利用丝印技术和聚二甲基硅氧烷（PDMS）材料制作微流控芯片，再与定制的具有加热或冷却功能的玻璃基微反应瓶组合而形成^18F微反应器。利用该微反应器合成^18F—FDG和^18F-氟乙酸盐（FAC），并测定2种产物的标记率和放化纯。结果高度集成化^18F微反应器的体积为40．0mm（长）×30．0mm（宽）×15．0mm（高），其中PDMS微流控芯片的体积为40．0mm（长）×30．0mm（宽）×6．0mm（高），气／液通道尺寸为0．3mm（宽）×50．0μm（高），微反应瓶的体积为200ILl，毛细管加热或冷却效果良好，可快速升温或降温。该微反应器实现了^18F-FDG和^18F-FAC的放射化学合成，其氟[^18F]化反应的标记率分别为92．5％和90．0％，产品放化纯均大于96％。结论该基于PDMS微流控芯片的^18F微反应器具有集成度高、总体积小、标记前体用量少的优点，可用于^18F-FDG和^18F—FAC的放射化学合成。

Objective Todevelop a polydimethylsiloxane （PDMS） microfluidic chip-based ^18F mi- croreactor for the preparation of ^18F-labeled probes. Methods The ^18F microreactor was composed of PDMS microfluidic chip and customized glass microvessel integrating with stainless capillary tube （D 0.6 mm） as heater/cooler. PDMS chips were fabricated by silk-screen printing technology, a traditional and easily acces- sible process, ^18F-FDG and ^18 F-fluoroacetate（FAC） were synthesized using the lS F microreactor. TLC was applied to measure the ^18F-labeling yield and the radiochemical purity of ^18F-FDG and ^18F-FAC. Results The size of PDMS chip was 40.0 mm （1）×30.0 mm （w）×6.0 mm （h） and the liquid/gas inside channel was 0.3 mm （w）×50.0 μm （h）. The customized glass microvessel was about 4.0 mm （D）×30.0 mm （h） with 200 μl of reaction volume. The capillary tube which wrapped around the microvessel functioned as a heater when electric current was provided, while as a cooler when compressed air went through. The inte- grated ＇SF microreactor with a total size of 40.0 mm （1） ×30.0 mm （w）×15.0 mm （h） was successfully used to prepare ISF-FDG and ^18F-FAC, whose radiochemical purity were both higher than 96% and lSF-la- beling yield was 92.5% and 90.0% respectively in the first fluorination step. Conclusions A PDMS mi- crofluidic chip-based ^18F microreactor is developed and successfully applied to prepare ＇SF-FDG and ^18F- FAC. It has the dual advantages of both microfluidc chip and traditional synthesis module and features of high integration, small total size and low consumption of labeling precursor.