A Microfluidic Flow-Chemistry System

The NanoTek is a modular, microfluidic synthesis system with the ability to  undertake both microscale and macroscale synthesis of both PET and SPECT imaging probes using a variety of isotopes. Modular components give the user maximum flexibility producing  tracers for both research and clinical applications. The NanoTek produces higher-yielding, higher-purity   compounds using substantially less starting materials than possible with conventional vial based reactors.  Initial optimization of synthesis conditions is typically completed in 1 – 2 minutes and the unique configuration of the system allows the user to undertake multiple syntheses in one day with one delivery of activity and using ugm quantities of reagent.

[ Animation: Automated Fluoride Drying and Resolubilization ]

Microfluidic Flow-Chemistry offers:

  • Speed –  Novel tracer optimization experiments are typically completed in one to two days.  Depending on the isotope as many as 30 to 50 reactions can be completed within one day.
  • Flexible – Research, Pre-Clinical and Clinical production (including dose-on-demand) processes can all be undertaken using the one platform.
  • Efficient – Final product yields have been reported as typically twice and in some instances as much as ten times possible using conventional systems. Precursor usage is often just 10% of that required conventionally and for biomolecules has been reported as being as low as 1%.
  • Expandable – The NanoTek is capable of including in line tracer concentration and purification steps  to maximize RAC and add MS characterization
  • Integration – In line purification and compound characterization can be seamlessly undertaken.
  • Versatility –  Publications and applications to date have reported successful tracer synthesis using a variety of isotopes including 11C, 13N, 18F, 99mTc, 111In, 211At. In excess of 40 novel tracers have been produced using the system.  All possible using one configuration.
  • Extended synthesis capabilities – The reactor(s) can operate at pressures up to 400psi (28 Bar) and temperatures in excess of 200C enabling experiments to be conducted under conditions not possible with conventional vial based systems including microwave reactors.
  • Purification using Analytical HPLC  –  Reduced product volumes and reduced by product formation, a consequence of microflow chemistry combined with post synthesis concentration enables tracers to be purified using analytical HPLC columns reducing final product volumes to 1ml or less and optimizing RAC for preclinical studies.
  • Microfluidic reactions using [11C]carbon monoxide solutions for the synthesis of a positron emission tomography radiotracerKealey, S.; Plisson, C.; Collier, T. L.; Long, N. J.; Husbands, S. M.; Martarello, L.; Gee, A. D.Org. Biomol. Chem., 2011. [Epub 25 March 2011]
  • Synthesis of hypoxia imaging agent 1-(5-deoxy-5-fluoro-α-d-arabinofuranosyl)-2-nitroimidazole using microfluidic technologyBouvet, V. R.; Wuest, M.; Wiebe, L. I.; Wuest, F.Nucl Med Biol., 2010 February, 38 (2):235-245. [Epub 3 December 2010]
  • Fast and high-yield microreactor syntheses of ortho-substituted [18F]fluoroarenes from reactions of [18F]fluoride ion with diaryliodonium saltsChun, J.-H.; Lu, S.; Lee, Y.-S.; Pike, V. W.J. Org. Chem., 2010, 75 (10):3332-3338.
  • Improved synthesis of 2'-deoxy-2'-[18F]-fluoro-1-beta-D-arabinofuranosyl-5-iodouracil   ([18F]-FIAU)Anderson, H.; Pillarsetty, N.; Cantorias, M.; Lewis, J.S.Nucl Med Biol. 2010 May, 37(4):439-42.
  • Microfluidic approach for fast labeling optimization and dose-on-demand implementation Pascali, G.; Mazzone, G.; Saccomanni, G.; Manera, C.; Salvadori, P. A.Nuclear Medicine and Biology, 2010; 37:547-555.
  • A microfluidic flow chemistry platform for organic synthesis: the Hofmann rearrangementPalmieri, A.; Ley, S. V.; Hammond, K.; Polyzos, A.; Baxendale, I. R.Tetrahedron Letters, 2009, 50 (26):3287-3289.
  • Single-step high-yield radiosynthesis and evaluation of a sensitive F-labeled ligand for imaging brain Peripheral benzodiazepine receptors with PETBriard, E.; Zoghbi, S. S.; Simeon, F. G.; Imaizumi, M.; Gourley, H.; Shetty, H. U.; Lu, S.; Fujita, M.; Innis, R. B.; Pike, V. W.J. Med. Chem., 2009 February 12, 52 (3):688-699.
  • Synthesis of [18F]fallypride in a micro-reactor: rapid optimization and multiple-production in small doses for micro-PET studiesLu, S.; Giamis, A. M.; Pike, V. W.Curr. Radiopharm., 2009;2(1):nihpa81093.