This
paper describes OsciDrop, a versatile chip-free droplet generator
used to produce size-tunable droplets on demand. Droplet generation
is fundamental to miniaturized analysis. We designed OsciDrop to segment
the fluid flowing out of the orifice of a disposable pipette tip into
droplets by oscillating its distal end underneath an immiscible continuous
phase. We described the theoretical model and investigated the effect
of flow rate, oscillating amplitude, frequency, and waveform on droplet
generation. Our study revealed a previously underexplored Weber number-dominated
regime that leverages inertial force instead of viscous force to generate
droplets. The same pipette tip allowed robust and deterministic generation
of monodisperse droplets with programmable sizes ranging from 200
pL to 2 μL by asymmetrical oscillation. We validated this platform
with two droplet-based nucleic acid amplification tests: a digital
loop-mediated isothermal amplification assay for absolute quantification
of African swine fever virus and a multi-volume digital polymerase
chain reaction assay for the high dynamic range measurement of human
genomic DNA. The OsciDrop method opens a facile avenue to miniaturization,
integration, and automation, exhibiting full accessibility for digital
molecular diagnostics.
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