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This report describes a straightforward but robust tubing method for connecting polydimethylsiloxane (PDMS) microfluidic devices to external equipment. The interconnection is irreversible and can sustain a pressure of up to 4.5 MPa that is characterized experimentally and theoretically. To demonstrate applications of this high-pressure tubing technique, we fabricate a semicircular microfluidic channel to implement a high-throughput, size-controlled synthesis of poly(lactic-co-glycolic acid) (PLGA) nanoparticles ranging from 55 to 135 nm in diameter. This microfluidic device allows for a total flow rate of 410 mL h−1, resulting in enhanced convective mixing which can be utilized to precipitate small size nanoparticles with a good dispersion. We expect that this tubing technique would be widely used in microfluidic chips for nanoparticle synthesis, cell manipulation, and potentially nanofluidic applications. [ABSTRACT FROM AUTHOR]