Performing multi-step chemical reactions in microliter-sized droplets by leveraging a simple passive transport mechanism

Wang, J.; Chao, Philip H.; Hanet, Sebastian; Dam, R. Michael van

doi:10.1039/c7lc01009e

Cited by 50 publications

(75 citation statements)

References 33 publications

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“…The system has applications in microfluidic radiochemistry, enabling the delivery of high amounts of activity into small-volume microreaction devices, e.g. based on droplet radiochemistry (Keng and van Dam, 2015; Wang et al, 2017), an area of active investigation in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

Automated concentration of [18F]fluoride into microliter volumes

Chao

Lazari

Hanet

et al. 2018

Applied Radiation and Isotopes

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Concentration of [F]fluoride has been mentioned in literature, however, reports have lacked details about system designs, operation, and performance. Here, we describe in detail a compact, fast, fully-automated concentration system based on a micro-sized strong anion exchange cartridge. The concentration of radionuclides enables scaled-up microfluidic synthesis. Our system can also be used to provide highly concentrated [F]fluoride with minimal water content. We demonstrate how the concentrator can produce varying concentrations of [F]fluoride for the macroscale synthesis of N-boc-5-[F]fluoroindole without an azeotropic drying process, while enabling high starting radioactivity. By appropriate choice of solid-phase resin, flow conditions, and eluent solution, we believe this approach can be extended beyond [F]fluoride to other radionuclides.

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Section: Discussionmentioning

confidence: 99%

Automated concentration of [18F]fluoride into microliter volumes

Chao

Lazari

Hanet

et al. 2018

Applied Radiation and Isotopes

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“…A particular configuration we are exploring is performing reactions in microliter-sized droplets on simple Teflon-coated silicon microfluidic chips, which has advantages of simple operation, low-cost disposable chips, and a compact system size, which reduces the necessary shielding. Previous work has shown application of this method for the rapid and efficient synthesis of [ 18 F]FDG and [ 18 F]Fallypride (Wang et al 2017). In this paper, we demonstrate further versatility of this approach by adapting the macroscale synthesis of O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) to this platform, and then use the produced [ 18 F]FET for pre-clinical imaging.…”

Section: Introductionmentioning

confidence: 88%

“…Radiochemistry was performed in droplet format on the surface of microfluidic chips comprising a silicon wafer with a patterned Teflon AF coating. The detailed fabrication was previously reported (Wang et al 2017). A combination of hydrophobic (Teflon) and hydrophilic (exposed silicon wafer) regions allows liquid droplets to be manipulated or maintained in a desired location to perform reactions.…”

Section: Microfluidic Systemsmentioning

confidence: 99%

“…The tapered pathways spontaneously transport reagent droplets from the periphery to the center of the chip. Complete details of this setup were reported previously (Wang et al 2017).…”

Section: Microfluidic Systemsmentioning

confidence: 99%

“…Of the several different microfluidic approaches reported in the last decade (Elizarov 2009;Keng and van Dam 2015;Miller et al 2010;Pascali and Matesic 2016;Rensch et al 2013), microvolume reaction approaches offer the greatest potential for reagent and instrument reductions (Dooraghi et al 2013;Elizarov et al 2010;Iwata et al 2018;Keng et al 2016;Lebedev et al 2012;Wang et al 2017). A particular configuration we are exploring is performing reactions in microliter-sized droplets on simple Teflon-coated silicon microfluidic chips, which has advantages of simple operation, low-cost disposable chips, and a compact system size, which reduces the necessary shielding.…”

Section: Introductionmentioning

confidence: 99%

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Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)

Lisova

Chen

Wang

et al. 2019

EJNMMI radiopharm. chem.

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Background: Conventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources. Using O-(2-[ 18 F]fluoroethyl)-Ltyrosine ([ 18 F]FET), we demonstrate that simple microvolume radiosynthesis techniques can improve the efficiency of production by consuming tiny amounts of precursor, and maintaining high molar activity of the tracers even with low starting activity. Procedures: The synthesis was carried out in microvolume droplets manipulated on a disposable patterned silicon "chip" affixed to a heater. A droplet of [ 18 F]fluoride containing TBAHCO 3 was first deposited onto a chip and dried at 100°C. Subsequently, a droplet containing 60 nmol of precursor was added to the chip and the fluorination reaction was performed at 90°C for 5 min. Removal of protecting groups was accomplished with a droplet of HCl heated at 90°C for 3 min. Finally, the crude product was collected in a methanol-water mixture, purified via analytical-scale radio-HPLC and formulated in saline. As a demonstration, using [ 18 F]FET produced on the chip, we prepared aliquots with different molar activities to explore the impact on preclinical PET imaging of tumor-bearing mice. Results: The microdroplet synthesis exhibited an overall decay-corrected radiochemical yield of 55 ± 7% (n = 4) after purification and formulation. When automated, the synthesis could be completed in 35 min. Starting with < 370 MBq of activity,~150 MBq of [ 18 F]FET could be produced, sufficient for multiple in vivo experiments, with high molar activities (48-119 GBq/μmol). The demonstration imaging study revealed the uptake of [ 18 F]FET in subcutaneous tumors, but no significant differences in tumor uptake as a result of molar activity differences (ranging 0.37-48 GBq/μmol) were observed. Conclusions: A microdroplet synthesis of [ 18 F]FET was developed demonstrating low reagent consumption, high yield, and high molar activity. The approach can be expanded to tracers other than [ 18 F]FET, and adapted to produce higher quantities of the tracer sufficient for clinical PET imaging.

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Lossless Fast Drop Self‐Transport on Anisotropic Omniphobic Surfaces: Origin and Elimination of Microscopic Liquid Residue

Huang

Liu

et al. 2019

Advanced Materials

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Surfaces enabling directional drop self‐transport have exceptional applications in digital microfluidics, chemical analysis, bioassay, and microreactor technology. While such properties have been obtained by engineering a surface with anisotropic microstructures, a microscopic liquid residue—though it might be invisible macroscopically—is generally left behind the transported drop, resulting in undesired transport loss and severely limiting practical applications of the surface. Here, the origin of microscopic liquid residue is studied by investigating directional drop self‐transport on anisotropic surfaces made of radially arranged omniphobic microstripes. It is revealed that the occurrence of a liquid residue is governed by a transport‐velocity‐dependent dynamic wetting mechanism involving the formation of entrained thin liquid films at high capillary numbers while the local dynamic receding contact angle vanishes. Rayleigh‐like breakup of the liquid films leads to the microscopic liquid residue. It is further shown that a liquid‐like coating featuring highly flexible molecular chains can effectively suppress the formation of entrained liquid films at high transport velocities, thereby facilitating lossless and fast drop self‐transport on anisotropic omniphobic surfaces.

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Performing multi-step chemical reactions in microliter-sized droplets by leveraging a simple passive transport mechanism

Cited by 50 publications

References 33 publications

Automated concentration of [18F]fluoride into microliter volumes

Automated concentration of [18F]fluoride into microliter volumes

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)

Lossless Fast Drop Self‐Transport on Anisotropic Omniphobic Surfaces: Origin and Elimination of Microscopic Liquid Residue

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