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Extracellular vesicles (EVs) have been identified as promising biomarkers for the noninvasive diagnosis of various diseases. However, challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low purities. Here, we report a high-yield ( > 90%) and rapid ( < 10 min) EV isolation method calledFLocculation viaOrbitalAcousticTrapping (FLOAT). The FLOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid droplets. By adding a thermoresponsive polymer flocculant, nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the droplet. We demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein, addressing a significant obstacle in the development of EV-based liquid biopsies. Due to its high-yield nature, FLOAT reduces biofluid starting volume requirements by a factor of 100 (from 20 mL to 200 µL), demonstrating its promising potential in point-of-care diagnostics.

 

Newly developed acoustic technologies are playing a transformational role in life science and biomedical applications ranging from the activation and inactivation of mechanosensitive ion channels for fundamental physiological processes to the development of contact-free, precise biofabrication protocols for tissue engineering and large-scale manufacturing of organoids. Here, we provide our perspective on the development of future acoustic technologies and their promise in addressing critical challenges in biomedicine.

 

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

The ability to precisely manipulate nano-objects on a large scale can enable the fabrication of materials and devices with tunable optical, electromagnetic, and mechanical properties. However, the dynamic, parallel manipulation of nanoscale colloids and materials remains a significant challenge. Here, we demonstrate acoustoelectronic nanotweezers, which combine the precision and robustness afforded by electronic tweezers with versatility and large-field dynamic control granted by acoustic tweezing techniques, to enable the massively parallel manipulation of sub-100 nm objects with excellent versatility and controllability. Using this approach, we demonstrated the complex patterning of various nanoparticles (e.g., DNAs, exosomes, ~3 nm graphene flakes, ~6 nm quantum dots, ~3.5 nm proteins, and ~1.4 nm dextran), fabricated macroscopic materials with nano-textures, and performed high-resolution, single nanoparticle manipulation. Various nanomanipulation functions, including transportation, concentration, orientation, pattern-overlaying, and sorting, have also been achieved using a simple device configuration. Altogether, acoustoelectronic nanotweezers overcome existing limitations in nano-manipulation and hold great potential for a variety of applications in the fields of electronics, optics, condensed matter physics, metamaterials, and biomedicine.

 

Traumatic brain injury (TBI) is a global cause of morbidity and mortality. Initial management and risk stratification of patients with TBI is made difficult by the relative insensitivity of screening radiographic studies as well as by the absence of a widely available, noninvasive diagnostic biomarker. In particular, a blood-based biomarker assay could provide a quick and minimally invasive process to stratify risk and guide early management strategies in patients with mild TBI (mTBI). Analysis of circulating exosomes allows the potential for rapid and specific identification of tissue injury. By applying acoustofluidic exosome separation—which uses a combination of microfluidics and acoustics to separate bioparticles based on differences in size and acoustic properties—we successfully isolated exosomes from plasma samples obtained from mice after TBI. Acoustofluidic isolation eliminated interference from other blood components, making it possible to detect exosomal biomarkers for TBI via flow cytometry. Flow cytometry analysis indicated that exosomal biomarkers for TBI increase in the first 24 h following head trauma, indicating the potential of using circulating exosomes for the rapid diagnosis of TBI. Elevated levels of TBI biomarkers were only detected in the samples separated via acoustofluidics; no changes were observed in the analysis of the raw plasma sample. This finding demonstrated the necessity of sample purification prior to exosomal biomarker analysis. Since acoustofluidic exosome separation can easily be integrated with downstream analysis methods, it shows great potential for improving early diagnosis and treatment decisions associated with TBI.

 

Optical imaging with nanoscale resolution and a large field of view is highly desirable in many research areas. Unfortunately, it is challenging to achieve these two features simultaneously while using a conventional microscope. An objective lens with a low numerical aperture (NA) has a large field of view but poor resolution. In contrast, a high NA objective lens will have a higher resolution but reduced field of view. In an effort to close the gap between these trade-offs, we introduce an acoustofluidic scanning nanoscope (AS-nanoscope) that can simultaneously achieve high resolution with a large field of view. The AS-nanoscope relies on acoustofluidic-assisted scanning of multiple microsized particles. A scanned 2D image is then compiled by processing the microparticle images using an automated big-data image algorithm. The AS-nanoscope has the potential to be integrated into a conventional microscope or could serve as a stand-alone instrument for a wide range of applications where both high resolution and large field of view are required. 

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.