Automated synthesis of gadopentetate dimeglumine through solid-liquid reaction in femtosecond laser fabricated microfluidic chips

Despite the continuously increased requirement on automated synthesis of medicines for distributed manufacturing and personal care, it remains a challenge to realize automated synthesis which requires solid-liquid phase reactions. In this work, we demonstrated an automated solid-liquid synthesis for gadopentetate dimeglumine, the most widely used magnetic resonance imaging (MRI) contrast agent. The high-efficiency reaction was performed in a 3D microfluidic chip which was fabricated by femtosecond laser micromachining. The structure of the chip realized 3D shear flow which was essential for highly efficient mixing and movement of the solid-liquid mixtures. Ultraviolet visible (UV–vis) spectrometer was employed for in-line analysis to help automation of this system. Comparing with the round-bottom flask system, this synthetic system showed significantly higher reaction rate, indicating the advantage of the 3D microfluidic technology in micro chemical engineering.

尽管分布式制造与个人护理领域对药物自动化合成的需求持续增长，但实现涉及固液相反应的自动化合成仍面临挑战。本研究展示了针对钆喷酸二甲葡胺（gadopentetate dimeglumine）——目前应用最广泛的磁共振成像（MRI）造影剂——的自动化固液合成方法。高效反应在通过飞秒激光微加工（femtosecond laser micromachining）制备的3D微流控芯片（3D microfluidic chip）中进行。该芯片的结构可产生3D剪切流，这对于固液混合物的高效混合与流动至关重要。紫外-可见分光光度计（UV–vis spectrometer）用于在线分析，助力系统自动化。与圆底烧瓶系统相比，该合成系统的反应速率显著提升，彰显了3D微流控技术在微化工领域的优势。