Precision acoustofluidics for life science

Abstract

Biological systems operate across multiple length scales, from molecular interactions and nanoparticle transport to cellular signaling and organism-level therapeutic responses. Achieving precise physical control across these scales remains a fundamental challenge in life science and biomedical engineering, as soft biological materials often exhibit stochastic transport, heterogeneous microenvironments, and weak coupling to external fields. This dissertation develops precision acoustofluidic strategies for engineering dynamic biointerfaces across scales, enabling controllable manipulation of biological processes from nanoparticles to living organisms.At the nanoscale, acoustic fields are engineered to manipulate nanoparticle–fluid interfaces beyond conventional diffraction limits. The Acoustofluidic Cryo-EM (ACE) platform employs deep-subwavelength acoustic streaming to homogenize and enrich nanoparticles within individual cryo-electron microscopy grid holes, improving particle distribution and imaging efficiency. At the cellular scale, the STREAM platform generates highly localized mechanical stimulation with high spatiotemporal resolution, enabling targeted stimulation of subcellular structures in tumor cells and providing a controllable tool for probing intracellular mechanotransduction. Extending these concepts to therapeutic applications, the PRISM strategy exploits engineered acoustic resonance at the liposome–cell interface to enhance nanoparticle internalization and therapeutic activation. In vivo studies in mouse tumor models demonstrate effective tumor suppression and immune activation.Together, these studies establish a multiscale acoustofluidic framework that bridges nanoparticle manipulation, subcellular mechanobiology, and in vivo therapeutic modulation. This work demonstrates how precision acoustic field engineering can serve as a versatile physical interface for life science, providing new opportunities for nanoscale imaging, cellular stimulation, and targeted biomedical therapies.