Journal of Labelled Compounds and Radiopharmaceuticals J Label Compd Radiopharm 2007; 50: 597–599. Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jlcr.1296 JLCR Short Research Article Separation of [ 18 F]fluoride ion from proton-irradiated [ 18 O]water within an EOF-driven micro-reactor powered by the Capilix Capella TM platform y SHUIYU LU 1, *, JAMES T. CLEMENTS 2 , MELIS JAN GILDE 3 , ALBERT PRAK 3 , PAUL WATTS 4 and VICTOR W. PIKE 1 1 Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3C346, Bethesda, MD 20892-1003, USA 2 NanoSciences Inc., 29 Skygate, Suite 200, Aliso Viejo, CA 92656, USA 3 CapiliX BV, De Veldmaat 10, SP32, 7522 NM Enschede, The Netherlands 4 Department of Chemistry, University of Hull, Cottingham Road, Hull HU6 7XR, UK Received 25 July 2006; Revised 22 January 2007; Accepted 31 January 2007 Keywords: micro-reactor; electroosmotic flow; PET; radiolabeling; [ 18 F]fluoride ion Introduction PET radiosyntheses in micro-reactors or microfluidic devices 1–5 has become of interest because these devices have the potential to deliver many advantages, such as: more efficient use of hot-cell space for production of multiple radiotracers; use of less non-radioactive precursor for saving precious material and a reduced separation challenge; highly controlled, reproducible and reliable radiotracer production; and the use of cheap, interchangeable, disposable and quality- assured radiochemistry processors. For the preparation of fluorine-18 labeled radio- pharmaceuticals, nucleophilic substitution reactions using cyclotron-produced [ 18 F]fluoride ion are most widely used. 6 [ 18 F]Fluoride ion is commonly produced as an aqueous solution in a [ 18 O]water target and must be dried to become adequately nucleophilic. The removal of water is normally carried out through azeotropic distillation with a solvent such as acetoni- trile. Although reliable and simple, the procedure is cumbersome to be adopted in micro-reactors. As described here we are exploring the electrokinetic properties of [ 18 F]fluoride ion and aim to develop a process for the preparation of reactive [ 18 F]fluoride ion in glass electroosmotic flow (EOF)-driven micro- reactors. Results and discussion Microfluidic capillary electrophoresis platform The CapiliX Capella TM capillary electrophoresis (CE) platform 7 (Figure 1) comprises a PSU-4 high-voltage power supply for EOF, a cartridge docking station linked to PSU-4 via high-voltage cables and a micro- fluidic chip cartridge in which the fluidic connections to the glass chip are sealed using Kalrez TM rubber O-rings. Glass micro-reactor Micro-reactor design R1 (Figure 2) has two flow restrictions between port 1 to junction and port 2 to junction, so that hydrodynamic flow can be minimized. There are no restrictions at the outlet to prevent any entrapment of air bubbles. At 500 V and 10 mm height difference between ports 1 and 4, the EOF-driven flow is 10 hydrodynamic flow. Typical experimental set up The channels of the micro-reactor were primed with 0.09% saline. Air bubbles inside the channel and rubber O-rings were carefully removed. Ports 1 and 2 were filled with additional saline (25 ml each). [ 18 F]Fluoride ion in H 2 18 O(100 mCi, 5–10 ml) was placed in port 4. Low radioactivity was used for safety Contract/grant sponsor: NIH (NIMH) y Proceedings of the Ninth International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, Edinburgh, 16–20 July 2006. *Correspondence to: Shuiyu Lu, PET Radiopharmaceutical Sciences, Molecular Imaging Branch, National Institute of Health Building 10, Room B3 C346, 10 Center Drive, Bethesda, MD 20892-1003, USA. E-mail: shuiyu.lu@mail.nih.gov Copyright # 2007 John Wiley & Sons, Ltd.