Oscillating microbubble array-based metamaterials (OMAMs) for rapid isolation of high-purity exosomes

Exosomes secreted by cells hold substantial potential for disease diagnosis and treatment. However, the rapid isolation of high-purity exosomes and their subpopulations from biofluids (e.g., undiluted whole blood) remains challenging. This study presents oscillating microbubble array-based metamaterials (OMAMs) for enabling the rapid isolation of high-purity exosomes and their subpopulations from biofluids without labeling or preprocessing. Particularly, leveraging acoustically excited microbubble oscillation, OMAMs can generate numerous acoustofluidic traps for filtering in-fluid micro/nanoparticles, thus allowing for removing bioparticles larger than exosomes to obtain high-purity (93%) exosomes from undiluted whole blood in ~3 minutes. Moreover, exosome subpopulations in different size ranges can be isolated by tuning the microbubble oscillation amplitude. Additionally, as each oscillating microbubble functions as an ultradeep subwavelength (~λ/186) acoustic amplifier and a nonlinear source, OMAMs can generate high-resolution complex acoustic energy patterns and tune the patterns by activating different-sized microbubbles at their distinct resonance frequencies.