Jones Jason, Do Viviann, Lu Yingqing, van Dam R Michael
Crump Institute of Molecular Imaging, University of California Los Angeles (UCLA),Los Angeles, CA, USA.
Physics and Biology in Medicine Interdepartmental Graduate Program, UCLA, USA.
Chem Eng J. 2023 Jul 15;468. doi: 10.1016/j.cej.2023.143524. Epub 2023 May 19.
The growing discovery and development of novel radiopharmaceuticals and radiolabeling methods requires an increasing capacity for radiochemistry experiments. However, such studies typically rely on radiosynthesizers designed for clinical batch production rather than research, greatly limiting throughput. Two general solutions are being pursued to address this: developing new synthesis optimization algorithms to minimize how many experiments are needed, and developing apparatus with enhanced experiment throughput. We describe here a novel high-throughput system based on performing arrays of droplet-based reactions at 10 μL volume scale in parallel. The automatic robotic platform can perform a set of 64 experiments in ~3 h (from isotope loading to crude product, plus sampling onto TLC plates), plus ~1 h for off-line radio-TLC analysis and radioactivity measurements, rather than the weeks or months that would be needed using a conventional system. We show the high repeatability and low crosstalk of the platform and demonstrate optimization studies for two F-labeled tracers. This novel automated platform greatly increases the practicality of performing arrays of droplet reactions by eliminating human error, vastly reducing tedium and fatigue, minimizing radiation exposure, and freeing up radiochemist time for other intellectually valuable pursuits.
新型放射性药物和放射性标记方法的不断发现与发展,对放射化学实验的能力需求日益增加。然而,此类研究通常依赖为临床批量生产而非研究设计的放射性合成仪,这极大地限制了通量。为解决这一问题,目前正在探索两种通用解决方案:开发新的合成优化算法以减少所需实验的数量,以及开发具有更高实验通量的仪器。我们在此描述一种新型高通量系统,该系统基于在10 μL体积规模上并行进行基于液滴的反应阵列。该自动机器人平台能够在约3小时内完成一组64个实验(从加载同位素到得到粗产物,再加上在薄层色谱板上取样),另外还需约1小时进行离线放射性薄层色谱分析和放射性测量,而使用传统系统则需要数周或数月时间。我们展示了该平台的高重复性和低串扰,并对两种氟标记示踪剂进行了优化研究。这种新型自动化平台通过消除人为误差、大幅减少乏味和疲劳、将辐射暴露降至最低,并为放射化学家腾出时间用于其他有智力价值的工作,极大地提高了进行液滴反应阵列的实用性。