Integrated microfluidic lab-on-a-chip systems for ¹⁸F radiotracer synthesis, purification and quality control

Objectives Dose-on-demand radiotracer production, whereby a single dose is generated using a compact synthesis unit with radioisotope from a mini-cyclotron or external supply is an interesting prospect for widening the availabilty of radiotracers. We aim to produce modules for lab-on-a-chip device design that can be used for isotope processing, synthesis and some routine quality control tests on a microfluidic scale.

Methods Modules for electrode trapping and release of [¹⁸F]fluoride, synthesis of [¹⁸F]FDG and purification were produced as prototypes using bespoke manufactured microfluidic glass chips with etched channels. Monolithic separation columns were made of a suitable size from silica and the functionality by chemical modification for the different purification and separation applications.Synthesis to validate the [¹⁸F]fluoride feed was carried out in a heated capillary loop. Spectroscopic quality control tests were developed using a simple on-chip absorbance-based system for performing QC tests rapidly (few min) with small volumes (<2 μL).

Results A process for highly efficient trap and release of [¹⁸F]fluoride from a low volume (< 200 μl) of aqueous solution allows trap and release into acetonitrile with an efficiency of up to 95% in both steps. Synthesis and purification using silica monolith columns designed for incoporation into microfluidic devices allowed isolation of pure product in good radiochemical yield (>80%). V-shaped plots were used to validate pH using absoprtion spectroscopy and solvent impurity using raman spectroscopy.

Conclusions Modules have been designed and tested for the synthesis of [¹⁸F]FDG. An efficient process for transfer of the [¹⁸F]fluoride into acetonitrile via electrode trapping allows synthesis of the [¹⁸F]FDG with high efficiency at low volumes was validated. Spearation modules using small (1-2 cm length) bespoke mopnolithic silica columns were used in the separations and some of the quality control tests were shown to be effective using both real samples and standards.

Research Support The authors thank the Daisy Appeal (grant no. DAhul0211) and the University of Hull (HEIF) for financial support. We would like to thank Dr Assem Allam for his generous support of this project.