Micro-chemical synthesis of molecular probes on an electronic microfluidic device.
We have developed an all-electronic digital microfluidic device for microscale chemical synthesis in organic solvents, operated by electrowetting-on-dielectric (EWOD). As an example of the principles, we demonstrate the multistep synthesis of [(18)F]FDG, the most common radiotracer for positron emission tomography (PET), with high and reliable radio-fluorination efficiency of [(18)F]FTAG (88 ± 7%, n = 11) and quantitative hydrolysis to [(18)F]FDG (> 95%, n = 11). We furthermore show that batches of purified [(18)F]FDG can successfully be used for PET imaging in mice and that they pass typical quality control requirements for human use (including radiochemical purity, residual solvents, Kryptofix, chemical purity, and pH). We report statistical repeatability of the radiosynthesis rather than best-case results, demonstrating the robustness of the EWOD microfluidic platform. Exhibiting high compatibility with organic solvents and the ability to carry out sophisticated actuation and sensing of reaction droplets, EWOD is a unique platform for performing diverse microscale chemical syntheses in small volumes, including multistep processes with intermediate solvent-exchange steps.
Crump Institute for Molecular Imaging, University of California, Los Angeles, CA 90095, USA.
Pei Yuin
PY
Keng
Supin
S
Chen
Huijiang
H
Ding
Saman
S
Sadeghi
Gaurav J
GJ
Shah
Alex
A
Dooraghi
Michael E
ME
Phelps
Nagichettiar
N
Satyamurthy
Arion F
AF
Chatziioannou
Chang-Jin
CJ
Kim
R Michael
RM
van Dam
D000818:Animals; D002855:Chromatography, Thin Layer; D004581:Electronics / Q000295:instrumentation*; D058874:Electrowetting; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18 / Q000138:chemical synthesis; D054879:Halogenation; D006801:Humans; D008223:Lymphoma / Q000000981:diagnostic imaging; D051379:Mice; D016513:Mice, SCID; D008832:Microchemistry / Q000295:instrumentation* / Q000379:methods*; D046210:Microfluidic Analytical Techniques; D015335:Molecular Probes / Q000138:chemical synthesis*; D049268:Positron-Emission Tomography; D011786:Quality Control; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
D005462:Fluorine Radioisotopes; D015335:Molecular Probes; D019788:Fluorodeoxyglucose F18