title: Radiolabelling diverse positron emission tomography (PET) tracers using a single digital microfluidic reactor chip.
abstract: Radiotracer synthesis is an ideal application for microfluidics because only nanogram quantities are needed for positron emission tomography (PET) imaging. Thousands of radiotracers have been developed in research settings but only a few are readily available, severely limiting the biological problems that can be studied in vivo via PET. We report the development of an electrowetting-on-dielectric (EWOD) digital microfluidic chip that can synthesize a variety of (18)F-labeled tracers targeting a range of biological processes by confirming complete syntheses of four radiotracers: a sugar, a DNA nucleoside, a protein labelling compound, and a neurotransmitter. The chip employs concentric multifunctional electrodes that are used for heating, temperature sensing, and EWOD actuation. All of the key synthesis steps for each of the four (18)F-labeled tracers are demonstrated and characterized with the chip: concentration of fluoride ion, solvent exchange, and chemical reactions. The obtained fluorination efficiencies of 90-95% are comparable to, or greater than, those achieved by conventional approaches.
authors.affiliation: Bioengineering Department, University of California, Los Angeles, CA 90095, USA. supin.chen@engineering.ucla.edu.
authors.forename: Supin
authors.initials: S
authors.lastname: Chen
authors.forename: Muhammad Rashed
authors.initials: MR
authors.lastname: Javed
authors.forename: Hee-Kwon
authors.initials: HK
authors.lastname: Kim
authors.forename: Jack
authors.initials: J
authors.lastname: Lei
authors.forename: Mark
authors.initials: M
authors.lastname: Lazari
authors.forename: Gaurav J
authors.initials: GJ
authors.lastname: Shah
authors.forename: R Michael
authors.initials: RM
authors.lastname: van Dam
authors.forename: Pei-Yuin
authors.initials: PY
authors.lastname: Keng
authors.forename: Chang-Jin C J
authors.initials: CJ
authors.lastname: Kim
mesh_terms: D002241:Carbohydrates / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D049268:Positron-Emission Tomography; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D052616:Solid Phase Extraction
chemical_list: D002241:Carbohydrates; D005462:Fluorine Radioisotopes; D011506:Proteins; D019275:Radiopharmaceuticals; D004247:DNA