Acoustofluidics for simultaneous droplet transport and centrifugation facilitating ultrasensitive biomarker detection

Trace biological sample detection is critical for the analysis of pathologies in biomedicine. Integration of microfluidic manipulation techniques typically strengthens biosensing performance. For instance, using isothermal amplification reactions to sense trace miRNA in peripheral circulation lacks a sufficiently complex pretreatment process that limits the sensitivity of on-chip detection. Herein we propose an orthogonal tunable acoustic tweezer (OTAT) to simultaneously actuate the transportation and centrifugation of μ-droplets on a single device. The OTAT enables diversified modes of droplet transportation such as unidirectional transport, multi-direction transport, round-trip transport, tilt angle movement, multi-droplet fusion, and continuous centrifugation of the dynamic droplets simultaneously. The multiplicity of modalities enables the focusing of a loaded analyte at the center of the droplet or constant rotation about the center axis of the droplet. We herein demonstrate the OTAT's ability to actuate transportation, fusion, and centrifugation-based pretreatment of two biological sample droplets loaded with miRNA biomarkers and multiple mixtures, as well as facilitating the increase of fluorescence detection sensitivity by an order of magnitude compared to traditional tube reaction methods. The results herein demonstrate the OTAT-based droplet acoustofluidic platform's ability to combine a wide range of biosensing mechanisms and provide a higher accuracy of detection for one-stop point-of-care disease diagnosis.