Dielectrophoretic bead-droplet reactor for solid-phase synthesis

Punnag Padhy (), Mohammad Asif Zaman, Michael Anthony Jensen (), Yao-Te Cheng, Yogi Huang, Mo Wu, Ludwig Galambos, Ronald Wayne Davis and Lambertus Hesselink ()
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Punnag Padhy: Stanford University
Mohammad Asif Zaman: Stanford University
Michael Anthony Jensen: Stanford University
Yao-Te Cheng: Stanford University
Yogi Huang: Stanford University
Mo Wu: Stanford University
Ludwig Galambos: Stanford University
Ronald Wayne Davis: Stanford University
Lambertus Hesselink: Stanford University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Solid-phase synthesis underpins many advances in synthetic and combinatorial chemistry, biology, and material science. The immobilization of a reacting species on the solid support makes interfacing of reagents an important challenge in this approach. In traditional synthesis columns, this leads to reaction errors that limit the product yield and necessitates excess consumption of the mobile reagent phase. Although droplet microfluidics can mitigate these problems, its adoption is fundamentally limited by the inability to controllably interface microbeads and reagent droplets. Here, we introduce Dielectrophoretic Bead-Droplet Reactor as a physical method to implement solid-phase synthesis on individual functionalized microbeads by encapsulating and ejecting them from microdroplets by tuning the supply voltage. Proof-of-concept demonstration of the enzymatic coupling of fluorescently labeled nucleotides onto the bead using this reactor yielded a 3.2-fold higher fidelity over columns through precise interfacing of individual microreactors and beads. Our work combines microparticle manipulation and droplet microfluidics to address a long-standing problem in solid-phase synthesis with potentially wide-ranging implications.

Date: 2024
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DOI: 10.1038/s41467-024-49284-z

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