Cell separation using tilted-angle standing surface acoustic waves

Separation of cells is a critical process for studying cell properties, disease diagnostics, and therapeutics. Cell sorting by acoustic waves offers a means to separate cells on the basis of their size and physical properties in a label-free, contactless, and biocompatible manner. The separation sensitivity and efficiency of currently available acoustic-based approaches, however, are limited, thereby restricting their widespread application in research and health diagnostics. In this work, we introduce a unique configuration of tilted-angle standing surface acoustic waves (taSSAW), which are oriented at an optimally designed inclination to the flow direction in the microfluidic channel. We demonstrate that this design significantly improves the efficiency and sensitivity of acoustic separation techniques. To optimize our device design, we carried out systematic simulations of cell trajectories, matching closely with experimental results. Using numerically optimized design of taSSAW, we successfully separated 2- and 10-µm-diameter polystyrene beads with a separation efficiency of ~99%, and separated 7.3- and 9.9-µm-polystyrene beads with an efficiency of ~97%. We illustrate that taSSAW is capable of effectively separating particles–cells of approximately the same size and density but different compressibility. Finally, we demonstrate the effectiveness of the present technique for biological–biomedical applications by sorting MCF-7 human breast cancer cells from nonmalignant leukocytes, while preserving the integrity of the separated cells. The method introduced here thus offers a unique route for separating circulating tumor cells, and for label-free cell separation with potential applications in biological research, disease diagnostics, and clinical practice.National Institutes of Health (U.S.) (Grant U01HL114476)National Institutes of Health (U.S.) (New Innovator Award 1DP2OD007209-01)National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (Grant DMR-0820404

Design of a Variable Thickness Plate to Focus Bending Waves

This paper describes the design of a thin plate whose thickness is tailored in order to focus bending waves to a desired location on the plate. Focusing is achieved by smoothly varying the thickness of the plate to create a type of lens, which focuses structural-borne energy. Damping treatment can then be positioned at the focal point to efficiently dissipate energy with a minimum amount of treatment. Numerical simulations of both bounded and unbounded plates show that the design is effective over a broad frequency range, focusing traveling waves to the same region of the plate regardless of frequency. This paper also quantifies the additional energy dissipated by local damping treatment installed on a variable thickness plate relative to a uniform plate

Optofluidic tunable microlens by manipulating the liquid meniscus using a flared microfluidic structure

We have designed, demonstrated, and characterized a simple, novel in-plane tunable optofluidic microlens. The microlens is realized by utilizing the interface properties between two different fluids: CaCl2solution and air. A constant contact angle of ∼90° is the pivotal factor resulting in the outward bowing and convex shape of the CaCl2 solution-air interface. The contact angle at the CaCl2 solution-air interface is maintained by a flared structure in the polydimethylsiloxane channel. The resulting bowing interface, coupled with the refractive index difference between the two fluids, results in effective in-plane focusing. The versatility of such a design is confirmed by characterizing the intensity of a traced beam experimentally and comparing the observed focal points with those obtained via ray-tracing simulations. With the radius of curvature conveniently controlled via fluid injection, the resulting microlens has a readily tunable focal length. This ease of operation, outstandingly low fluid usage, large range tunable focal length, and in-plane focusing ability make this lens suitable for many potential lab-on-a-chip applications such as particle manipulation, flow cytometry, and in-plane optical trapping

Single-Shot Characterization of Enzymatic Reaction Constants <i>K</i>_m and <i>k</i>_cat by an Acoustic-Driven, Bubble-Based Fast Micromixer

In this work we present an acoustofluidic approach for rapid, single-shot characterization of enzymatic reaction constants <i>K</i>_m and <i>k</i>_cat. The acoustofluidic design involves a bubble anchored in a horseshoe structure which can be stimulated by a piezoelectric transducer to generate vortices in the fluid. The enzyme and substrate can thus be mixed rapidly, within 100 ms, by the vortices to yield the product. Enzymatic reaction constants <i>K</i>_m and <i>k</i>_cat can then be obtained from the reaction rate curves for different concentrations of substrate while holding the enzyme concentration constant. We studied the enzymatic reaction for β-galactosidase and its substrate (resorufin-β-D-galactopyranoside) and found <i>K</i>_m and <i>k</i>_cat to be 333 ± 130 μM and 64 ± 8 s^–1, respectively, which are in agreement with published data. Our approach is valuable for studying the kinetics of high-speed enzymatic reactions and other chemical reactions

An integrated, multiparametric flow cytometry chip using “microfluidic drifting” based three-dimensional hydrodynamic focusing

In this work, we demonstrate an integrated, single-layer, miniature flow cytometry device that is capable of multi-parametric particle analysis. The device integrates both particle focusing and detection components on-chip, including a “microfluidic drifting” based three-dimensional (3D) hydrodynamic focusing component and a series of optical fibers integrated into the microfluidic architecture to facilitate on-chip detection. With this design, multiple optical signals (i.e., forward scatter, side scatter, and fluorescence) from individual particles can be simultaneously detected. Experimental results indicate that the performance of our flow cytometry chip is comparable to its bulky, expensive desktop counterpart. The integration of on-chip 3D particle focusing with on-chip multi-parametric optical detection in a single-layer, mass-producible microfluidic device presents a major step towards low-cost flow cytometry chips for point-of-care clinical diagnostics

Class and the northern seas

SIGLEAvailable from British Library Document Supply Centre-DSC:9348.749(7) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

An On-Chip, Multichannel Droplet Sorter Using Standing Surface Acoustic Waves

The emerging field of droplet microfluidics requires effective on-chip handling and sorting of droplets. In this work, we demonstrate a microfluidic device that is capable of sorting picoliter water-in-oil droplets into multiple outputs using standing surface acoustic waves (SSAW). This device integrates a single-layer microfluidic channel with interdigital transducers (IDTs) to achieve on-chip droplet generation and sorting. Within the SSAW field, water-in-oil droplets experience an acoustic radiation force and are pushed toward the acoustic pressure node. As a result, by tuning the frequency of the SSAW excitation, the position of the pressure nodes can be changed and droplets can be sorted to different outlets at rates up to 222 droplets s^–1. With its advantages in simplicity, controllability, versatility, noninvasiveness, and capability to be integrated with other on-chip components such as droplet manipulation and optical detection units, the technique presented here could be valuable for the development of droplet-based micro total analysis systems (μTAS)

An On-Chip, Multichannel Droplet Sorter Using Standing Surface Acoustic Waves

The emerging field of droplet microfluidics requires effective on-chip handling and sorting of droplets. In this work, we demonstrate a microfluidic device that is capable of sorting picoliter water-in-oil droplets into multiple outputs using standing surface acoustic waves (SSAW). This device integrates a single-layer microfluidic channel with interdigital transducers (IDTs) to achieve on-chip droplet generation and sorting. Within the SSAW field, water-in-oil droplets experience an acoustic radiation force and are pushed toward the acoustic pressure node. As a result, by tuning the frequency of the SSAW excitation, the position of the pressure nodes can be changed and droplets can be sorted to different outlets at rates up to 222 droplets s^–1. With its advantages in simplicity, controllability, versatility, noninvasiveness, and capability to be integrated with other on-chip components such as droplet manipulation and optical detection units, the technique presented here could be valuable for the development of droplet-based micro total analysis systems (μTAS)