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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.

 

Manipulation of microparticles and bio-samples is a critical task in many research and clinical settings. Recently, acoustic based methods have garnered significant attention due to their relatively simple designs, and biocompatible and precise manipulation of small objects. Herein, we introduce a flexural wave based acoustofluidic manipulation platform that utilizes low-frequency (4–6 kHz) commercial buzzers to achieve dynamic particle concentration and translation in an open fluid well. The device has two primary modes of functionality, wherein particles can be concentrated in pressure nodes that are present on the bottom surface of the device, or particles can be trapped and manipulated in streaming vortices within the fluid domain; both of these functions result from flexural mode vibrations that travel from the transducers throughout the device. Throughout our research, we numerically and experimentally explored the wave patterns generated within the device, investigated the particle concentration phenomenon, and utilized a phase difference between the two transducers to achieve precision movement of fluid vortices and the entrapped particle clusters. With its simple, low-cost nature and open fluidic chamber design, this platform can be useful in many biological, biochemical, and biomedical applications, such as tumor spheroid generation and culture, as well as the manipulation of embryos. 

Abstract Density and mechanical properties (e.g., compressibility or bulk modulus) are important cellular biophysical markers. As such, developing a method to separate cells directly based on these properties can benefit various applications including biological research, diagnosis, prognosis, and therapeutics. As a potential solution, surface acoustic wave (SAW)-based cell separation has demonstrated advantages in terms of biocompatibility and compact device size. However, most SAW-reliant cell separations are achieved using an entangled effect of density, various mechanical properties, and size. In this work, we demonstrate SAW-based separation of cells/particles based on their density and compressibility, irrespective of their sizes, by manipulating the acoustic properties of the fluidic medium. Using our platform, SAW-based separation is achieved by varying the dimensions of the microfluidic channels, the wavelengths of acoustic signals, and the properties of the fluid media. Our method was applied to separate paraformaldehyde-treated and fresh Hela cells based on differences in mechanical properties; a recovery rate of 85% for fixed cells was achieved. It was also applied to separate red blood cells (RBCs) and white blood cells (WBCs) which have different densities. A recovery rate of 80.5% for WBCs was achieved. 

Whether reagents and samples need to be combined to achieve a desired reaction, or precise concentrations of solutions need to be mixed and delivered downstream, thorough mixing remains a critical step in many microfluidics-based biological and chemical assays and analyses. To achieve complete mixing of fluids in microfluidic devices, researchers have utilized novel channel designs or active intervention to facilitate mass transport and exchange of fluids. However, many of these solutions have a major limitation: their design inherently limits their operational throughput; that is, different designs work at specific flow rates, whether that be low or high ranges, but have difficulties outside of their tailored design regimes. In this work, we present an acoustofluidic mixer that is capable of achieving efficient, thorough mixing across a broad range of flow rates (20–2000 μL min −1 ) using a single device. Our mixer combines active acoustofluidic mixing, which is responsible for mixing fluids at lower flow rates, with passive hydrodynamic mixing, which accounts for mixing fluids at higher flow rates. The mechanism, functionality, and performance of our acoustofluidic device are both numerically and experimentally validated. Additionally, the real-world potential of our device is demonstrated by synthesizing polymeric nanoparticles with comparable sizes over a two-order-of-magnitude wide range of flow rates. This device can be valuable in many biochemical, biological, and biomedical applications. For example, using our platform, one may synthesize nanoparticles/nanomaterials at lower flow rates to first identify optimal synthesis conditions without having to waste significant amounts of reagents, and then increase the flow rate to perform high-throughput synthesis using the optimal conditions, all using the same single device and maintaining performance. 

In this article, we demonstrate an acoustofluidic device for cell lysis using the acoustic streaming effects induced by acoustically oscillating sharp-edged structures. The acoustic streaming locally generates high shear forces that can mechanically rupture cell membranes. With the acoustic-streaming-derived shear forces, our acoustofluidic device can perform cell lysis in a continuous, reagent-free manner, with a lysis efficiency of more than 90% over a range of sample flow rates. We demonstrate that our acoustofluidic lysis device works well on both adherent and non-adherent cells. We also validate it using clinically relevant samples such as red blood cells infected with malarial parasites. Additionally, the unique capability of our acoustofluidic device was demonstrated by performing downstream protein analysis and gene profiling without additional washing steps post-lysis. Our device is simple to fabricate and operate while consuming a relatively low volume of samples. These advantages and other features including the reagent-free nature and controllable lysis efficiency make our platform valuable for many biological and biomedical applications, particularly for the development of point-of-care platforms. 

The valley degree of freedom in crystals offers great potential for manipulating classical waves, however, few studies have investigated valley states with complex wavenumbers, valley states in graded systems, or dispersion tuning for valley states. Here, we present tunable valley phononic crystals (PCs) composed of hybrid channel-cavity cells with three tunable parameters. Our PCs support valley states and Dirac cones with complex wavenumbers. They can be configured to form chirped valley PCs in which edge modes are slowed to zero group velocity states, where the energy at different frequencies accumulates at different designated locations. They enable multiple functionalities, including tuning of dispersion relations for valley states, robust routing of surface acoustic waves, and spatial modulation of group velocities. This work may spark future investigations of topological states with complex wavenumbers in other classical systems, further study of topological states in graded materials, and the development of acoustic devices.