Oscillating microbubble array–based metamaterials (OMAMs) for rapid isolation of high-purity exosomes
Xinjia Li, Zhiting Deng, Wenjun Zhang, Wei Zhou, Xiufang Liu, Hao Quan, Jiali Li, Peng-Qi Li, Yingyin Li, Hu Cai, Fei Li, Lili Niu, Zhenhua Tian, Long Meng, Hairong Zheng
Abstract
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.