Robust temperature change rate actuated valving and switching for highly integrated centrifugal microfluidics.

We present new unit operations for valving and switching in centrifugal microfluidics that are actuated by a temperature change rate (TCR) and controlled by the rotational frequency. Implementation is realized simply by introducing a comparatively large fluidic resistance to an air vent of a fluidic structure downstream of a siphon channel. During temperature decrease at a given TCR, the air pressure inside the downstream structure decreases and the fluidic resistance of the air vent slows down air pressure compensation allowing a thermally induced underpressure to build up temporarily. Thereby the rate of temperature change determines the time course of the underpressure for a given geometry. The thermally induced underpressure pulls the liquid against a centrifugal counterpressure above a siphon crest, which triggers the valve or switch. The centrifugal counterpressure (adjusted by rotation) serves as an independent control parameter to allow or prevent valving or switching at any TCR. The unit operations are thus compatible with any temperature or centrifugation protocol prior to valving or switching. In contrast to existing methods, this compatibility is achieved at no additional costs: neither additional fabrication steps nor additional disk space or external means are required besides global temperature control, which is needed for the assay. For the layout, an analytical model is provided and verified. The TCR actuated unit operations are demonstrated, first, by a stand-alone switch that routes the liquid to either one of the two collection chambers (n = 6) and, second, by studying the robustness of TCR actuated valving within a microfluidic cartridge for highly integrated nucleic acid testing. Valving could safely be prevented during PCR by compensating the thermally induced underpressure of 3.52 kPa with a centrifugal counterpressure at a rotational frequency of 30 Hz with a minimum safety range to valving of 2.03 kPa. Subsequently, a thermally induced underpressure of 2.55 kPa was utilized for robust siphon valving at 3 Hz with a minimum safety range of 2.32 kPa.