(A) EWOD microchip with four concentric heaters (dashed circle) with a maximum volume of 17 μL. Inset shows magnified area of the heater with four concentric individually controlled resistive heating rings. (B) Schematic side view of the EWOD chip sandwiching a reaction droplet between two plates coated with ITO electrodes, a dielectric layer, and a hydrophobic layer of Cytop (not to scale).

(A) Stack radio-TLC chromatogram of the crude [¹⁸F]TAG (green trace), crude [¹⁸F]FDG (blue trace), and purified [¹⁸F]FDG (red trace) from a typical on-chip synthesis. The radio-TLC profile of the purified [¹⁸F]FDG showed > 99% chemical purity after passing through the custom made cartridge shown in (B), with 88% purification efficiency. (B) A schematic diagram of the custom made cartridge comprised of ion retardation, cation exchange, neutral alumina and C-18 resins packed within a 760 μm diameter perfluoroalkoxy tube.

Sequence of photograph images with and the corresponding Cerenkov images (blue background) and the synthetic scheme of the multistep radiosynthesis performed on EWOD. For clarification, the heater region is outlined with a red circle, the droplet is outlined with white dashes, the blue arrow illustrates the needle position and direction of nitrogen flow, and the activation of the heater is indicated by the thermometer symbol with adjacent temperature. (i) Edge loading of the [¹⁸F]KF/K_2.2.2 complex onto the chip and transport to the heater via EWOD; (ii) Concentration of the [¹⁸F]KF/K_2.2.2 complex via evaporation; (iii) Exchange of solvent to anhydrous MeCN followed by several cycles of azeotropic distillation; (iv) Loading of mannose triflate (precursor) and mixing with the dried [¹⁸F]KF/K_2.2.2 by heating at moderate temperature; followed by fluorination of mannose triflate; (v) Addition of droplets containing a mixture of HCl/MeCN to the crude [¹⁸F]FTAG intermediate to perform hydrolysis to form [¹⁸F]FDG. The color legend on the right indicates the brightness of the Cerenkov light. Qualitatively, Cerenkov images confirmed that the radioactivity is always confined to the droplet in steps where liquid is present in every step of the synthesis.

Small animal PET and CT images of a mouse bearing a lymphoma xenograft (right shoulder) after administration of [¹⁸F]FDG prepared on EWOD chip (left), and [¹⁸F]FDG prepared at the UCLA Biomedical Cyclotron facility (right). Injections and static scans (10 min duration, 1 h postinjection) were performed on the same mouse on consecutive days.