Antoine Daridon

Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics.

Microreactor technology has shown potential for optimizing synthetic efficiency, particularly in preparing sensitive compounds. We achieved the synthesis of an [18F]fluoride-radiolabeled molecular imaging probe, 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG), in an integrated microfluidic device. Five sequential processes—[18F]fluoride concentration, water evaporation, radiofluorination, solvent exchange, and hydrolytic deprotection—proceeded with high radio-chemical yield and purity and with shorter synthesis time relative to conventional automated synthesis. Multiple doses of [18F]FDG for positron emission tomography imaging studies in mice were prepared. These results, which constitute a proof of principle for automated multistep syntheses at the nanogram to microgram scale, could be generalized to a range of radiolabeled substrates.

Absolute quantitative detection of ABL tyrosine kinase domain point mutations in chronic myeloid leukemia using a novel nanofluidic platform and mutation-specific PCR

Absolute quantitative detection of ABL tyrosine kinase domain point mutations in chronic myeloid leukemia using a novel nanofluidic platform and mutation-specific PCR

Design and Optimization of Coin-Shaped Microreactor Chips for PET Radiopharmaceutical Synthesis

An integrated elastomeric microfluidic device, with a footprint the size of a postage stamp, has been designed and optimized for multistep radiosynthesis of PET tracers. Methods: The unique architecture of the device is centered around a 5-μL coin-shaped reactor, which yields reaction efficiency and speed from a combination of high reagent concentration, pressurized reactions, and rapid heat and mass transfer. Its novel features facilitate mixing, solvent exchange, and product collection. New mixing mechanisms assisted by vacuum, pressure, and chemical reactions are exploited. Results: The architecture of the reported reactor is the first that has allowed batch-mode microfluidic devices to produce radiopharmaceuticals of sufficient quality and quantity to be validated by in vivo imaging. Conclusion: The reactor has the potential to produce multiple human doses of 18F-FDG; the most impact, however, is expected in the synthesis of PET radiopharmaceuticals that can be made only with low yields by currently available equipment.

Flow optimization study of a batch microfluidics PET tracer synthesizing device

We present numerical modeling and experimental studies of flow optimization inside a batch microfluidic micro-reactor used for synthesis of human-scale doses of Positron Emission Tomography (PET) tracers. Novel techniques are used for mixing within, and eluting liquid out of, the coin-shaped reaction chamber. Numerical solutions of the general incompressible Navier Stokes equations along with time-dependent elution scalar field equation for the three dimensional coin-shaped geometry were obtained and validated using fluorescence imaging analysis techniques. Utilizing the approach presented in this work, we were able to identify optimized geometrical and operational conditions for the micro-reactor in the absence of radioactive material commonly used in PET related tracer production platforms as well as evaluate the designed and fabricated micro-reactor using numerical and experimental validations.

A Programmable Cell Assay Platform for Kinetic Studies of a Single Cell

We demonstrate the passive capture of a single cell in a specific area of a microfluidic chip and the active delivery of reagents or compounds to that cell. This delivery of reagents and the wash steps are very rapid. The chip can be used to perform many different types of cell-based assays, such as Ca++ flux and apoptosis. Both mix-and-measure and heterogeneous assays can be performed in real-time. The trap can be used serially for multiple assays, because a trapped cell can be dispensed after the assay either to waste or to a downstream function, such as a region for further culturing.