Micro-chemical synthesis of molecular probes on an electronic microfluidic device
Micro-chemical synthesis of molecular probes on an electronic microfluidic device
复制标题
DOI：
10.1073/pnas.1117566109
复制
发表时间：
2012-01-17
影响因子：
11.1
通讯作者：
van Dama, R. Michael
中科院分区：
文献类型：
--
作者：
Keng, Pei Yuin;Chen, Supin;van Dama, R. Michael
我们开发了一种全电子数字微流控装置，用于在有机溶剂中进行微尺度化学合成，该装置采用电介质电润湿（EWOD）操作。作为原理的一个例子，我们展示了[F-18]FDG的多步合成，[F-18]FDG是正电子发射断层扫描（PET）最常见的放射性示踪剂，具有高可靠的放射性氟化效率[F-18] FTAG （88 +/- 7%, n = 11）和定量水解成[F-18]FDG （>95%, n = 11）。我们进一步表明，纯化的[F-18]FDG批次可以成功地用于小鼠PET成像，并且它们通过了人类使用的典型质量控制要求（包括放射化学纯度、残留溶剂、Kryptofix、化学纯度和pH值）。我们报告了放射性合成的统计可重复性，而不是最佳结果，证明了EWOD微流控平台的鲁棒性。EWOD具有与有机溶剂的高相容性以及对反应液滴进行复杂驱动和传感的能力，是一个独特的平台，可以在小体积内进行各种微尺度化学合成，包括具有中间溶剂交换步骤的多步骤过程。
We have developed an all-electronic digital microfluidic device for microscale chemical synthesis in organic solvents, operated by electrowetting-on-dielectric (EWOD). As an example of the principles, we demonstrate the multistep synthesis of [F-18]FDG, the most common radiotracer for positron emission tomography (PET), with high and reliable radio-fluorination efficiency of [F-18] FTAG (88 +/- 7%, n = 11) and quantitative hydrolysis to [F-18]FDG (>95%, n = 11). We furthermore showthat batches of purified [F-18]FDG can successfully be used for PET imaging in mice and that they pass typical quality control requirements for human use (including radiochemical purity, residual solvents, Kryptofix, chemical purity, and pH). We report statistical repeatability of the radiosynthesis rather than bestcase results, demonstrating the robustness of the EWOD microfluidic platform. Exhibiting high compatibility with organic solvents and the ability to carry out sophisticated actuation and sensing of reaction droplets, EWOD is a unique platform for performing diverse microscale chemical syntheses in small volumes, including multistep processes with intermediate solvent-exchange steps.