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sEV subpopulations and nanoparticles are directly fractionated via acoustic virtual wave-pillars without any sample preprocessing. 

Modern biomedical research and preclinical pharmaceutical development rely heavily on the phenotyping of small vertebrate models for various diseases prior to human testing. In this article, we demonstrate an acoustofluidic rotational tweezing platform that enables contactless, high-speed, 3D multispectral imaging and digital reconstruction of zebrafish larvae for quantitative phenotypic analysis. The acoustic-induced polarized vortex streaming achieves contactless and rapid (~1 s/rotation) rotation of zebrafish larvae. This enables multispectral imaging of the zebrafish body and internal organs from different viewing perspectives. Moreover, we develop a 3D reconstruction pipeline that yields accurate 3D models based on the multi-view images for quantitative evaluation of basic morphological characteristics and advanced combinations of metrics. With its contactless nature and advantages in speed and automation, our acoustofluidic rotational tweezing system has the potential to be a valuable asset in numerous fields, especially for developmental biology, small molecule screening in biochemistry, and pre-clinical drug development in pharmacology.

 

Advances in lab-on-a-chip technologies are driven by the pursuit of programmable microscale bioreactors or fluidic processors that mimic electronic functionality, scalability, and convenience. However, few fluidic mechanisms allow for basic logic operations on rewritable fluidic paths due to cross-contamination, which leads to random interference between “fluidic bits” or droplets. Here, we introduce a mechanism that allows for contact-free gating of individual droplets based on the scalable features of acoustic streaming vortices (ASVs). By shifting the hydrodynamic equilibrium positions inside interconnected ASVs with multitonal electrical signals, different functions such as controlling the routing and gating of droplets on rewritable fluidic paths are demonstrated with minimal biochemical cross-contamination. Electrical control of this ASV-based mechanism allows for unidirectional routing and active gating behaviors, which can potentially be scaled to functional fluidic processors that can regulate the flow of droplets in a manner similar to the current in transistor arrays.