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.
Keyphrases
- high throughput
- nucleic acid
- single cell
- single molecule
- endothelial cells
- loop mediated isothermal amplification
- high frequency
- minimally invasive
- sensitive detection
- gene expression
- atomic force microscopy
- dna methylation
- high resolution
- induced pluripotent stem cells
- highly efficient
- circulating tumor cells
- quantum dots
- mass spectrometry
- pluripotent stem cells