Monodisperse drops templated by 3D-structured microparticles – a foundation for sensitive compartmentalized molecular and cell-based assays with minimal instrumentation

The ability to create uniform subnanoliter compartments using microfluidic control has enabled new approaches for analysis of single cells and molecules. However, specialized instruments or expertise has been required, slowing the adoption of these cutting-edge applications. UCLA researchers show that three dimensional–structured microparticles with sculpted surface chemistries template uniformly sized aqueous drops when simply mixed with two immiscible fluid phases. In contrast to traditional emulsions, particle-templated drops of a controlled volume occupy a minimum in the interfacial energy of the system, such that a stable monodisperse state results with simple and reproducible formation conditions. The researchers describe techniques to manufacture microscale drop-carrier particles and show that emulsions created with these particles prevent molecular exchange, concentrating reactions within the drops, laying a foundation for sensitive compartmentalized molecular and cell-based assays with minimal instrumentation.

Simultaneous formation of monodisperse dropicles by
batch mixing and centrifugation operations

DCPs are manufactured with poly(ethylene glycol) (PEG) and poly(propylene glycol) (PPG) as the hydrophilic and hydrophobic layers, respectively. A collection of DCPs is shown suspended in ethanol on the left. Dropicles with aqueous solution containing fluorescent dye in a toluene continuous phase are shown in the bottom of a vial on the right with brightfield and fluorescence channels. Dropicles are generated in the filled configuration, ivmin with minimal system energy. Insets in the right show a single dropicle in brightfield and fluorescein isothiocyanate (FITC) channels. Scale bars, 500 μm.

Wu CY, Ouyang M, Wang B, de Rutte J, Joo A, Jacobs M, Ha K, Bertozzi AL, Di Carlo D. (2020) Monodisperse drops templated by 3D-structured microparticles. Sci Adv 6(45):eabb9023. [article]

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