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用于放射化学应用的耐溶剂型微流控芯片平台。

A solvent resistant lab-on-chip platform for radiochemistry applications.

机构信息

GE Global Research, Freisinger Landstrasse 50, 85748 Garching bei Munich, Germany.

出版信息

Lab Chip. 2014 Jul 21;14(14):2556-64. doi: 10.1039/c4lc00076e.

Abstract

The application of microfluidics to the synthesis of Positron Emission Tomography (PET) tracers has been explored for more than a decade. Microfluidic benefits such as superior temperature control have been successfully applied to PET tracer synthesis. However, the design of a compact microfluidic platform capable of executing a complete PET tracer synthesis workflow while maintaining prospects for commercialization remains a significant challenge. This study uses an integral system design approach to tackle commercialization challenges such as the material to process compatibility with a path towards cost effective lab-on-chip mass manufacturing from the start. It integrates all functional elements required for a simple PET tracer synthesis into one compact radiochemistry platform. For the lab-on-chip this includes the integration of on-chip valves, on-chip solid phase extraction (SPE), on-chip reactors and a reversible fluid interface while maintaining compatibility with all process chemicals, temperatures and chip mass manufacturing techniques. For the radiochemistry device it includes an automated chip-machine interface enabling one-move connection of all valve actuators and fluid connectors. A vial-based reagent supply as well as methods to transfer reagents efficiently from the vials to the chip has been integrated. After validation of all those functional elements, the microfluidic platform was exemplarily employed for the automated synthesis of a Gastrin-releasing peptide receptor (GRP-R) binding the PEGylated Bombesin BN(7-14)-derivative ([(18)F]PESIN) based PET tracer.

摘要

微流控技术在正电子发射断层扫描(PET)示踪剂合成中的应用已经探索了十多年。微流控的优势,如卓越的温度控制,已经成功地应用于 PET 示踪剂合成。然而,设计一个能够执行完整的 PET 示踪剂合成工作流程的紧凑微流控平台,同时保持商业化的前景,仍然是一个重大挑战。本研究采用整体系统设计方法来解决商业化挑战,例如从一开始就与材料处理兼容性相关的成本效益高的芯片级大规模制造的途径。它将简单的 PET 示踪剂合成所需的所有功能元件集成到一个紧凑的放射化学平台中。对于芯片实验室,这包括集成芯片上阀、芯片上固相萃取(SPE)、芯片上反应器和可逆流体界面,同时与所有工艺化学品、温度和芯片大规模制造技术兼容。对于放射化学装置,它包括一个自动化的芯片-机器接口,能够实现所有阀门执行器和流体连接器的一键连接。已经集成了基于小瓶的试剂供应以及从小瓶中高效转移试剂到芯片的方法。在验证了所有这些功能元件后,该微流控平台被用于自动化合成胃泌素释放肽受体(GRP-R)结合聚乙二醇化蛙皮素 BN(7-14)-衍生物 ([(18)F]PESIN)的基于 PET 的示踪剂。

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