Background

Compact devices that can perform rapid and complex analysis on minute biological samples with minimal reagents are appealing for both field and benchtop applications. Sample preparation for such devices, however, remains a critical challenge. For successful analysis of clinical and environmental samples, pre-processing is most often performed on the benchtop and entails mostly manual, time-consuming and labor intensive techniques. The coming together of the scaling advantages inherent in microtechnology, with the need to speed up, automate, and integrate sample preparation and analysis, has led to intense effort in the development of microfluidic platforms for a variety of tasks, from particle filtration, cell sorting and separation, to surface-based assays and purification of biological analytes. Concurrently with the tremendous proliferation of microfluidic technologies over the last 20 years, rapid progress has been made in adapting ultrasound for sample manipulation in sub-millimeter-scale fluidic networks. Acoustofluidic approaches combine non-contact handling of fluid-suspended particles with the potential for high-throughput continuous processing.

Using these principles, LLNL has developed a fast, continuous-flow separation device for automated sample processing. A high-throughput, flow-through viral enrichment technology such as this acoustofluidic device can be advantageous for reducing hands-on time while enriching for the viral content of samples such as serum (clinical), wastewater (industrial), and sea-water (environmental) for subsequent analysis. Recently, LLNL scientists reported high-throughput separation of particles and T lymphocytes by altering net sonic velocity to reposition acoustic pressure nodes in a simple two-channel device, further described below.

Description

LLNL researchers have developed an acoustofluidic device design consisting of a silicon and glass chip bonded to a piezoelectric plate. The acoustic microfluidic chip design is optimized using numerical modelling for maximal pressure standing wave amplitude, and its unique configuration with subdivided channels enables high-throughput operation and customized placement of the acoustic pressure node. Experimental verification has demonstrated high-throughput size-separation of cells and viral particles, and label-free purification of biological samples.

Refer to the following publications for additional information on the research.

Efficient coupling of acoustic modes in microfluidic channel devices, Lab Chip, 2015, 15, 3192

Spatial tuning of acoustofluidic pressure nodes by altering net sonic velocity enables high-throughput, efficient cell sorting, Lab Chip, 2015, 15, 1000.

Acoustic focusing with engineered node locations for high-performance microfluidic particle separation, Analyst, 2014, 139, 1192

Continuously Variable Node Position in a High-Throughput Acoustofluidic Device, 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 26-30, 2014

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Advantages
  • Increased Flow.The LLNL device is fabricated from silicon and glass, allowing for 1-2 orders of magnitude greater volumetric throughput and linear flow velocity.
  • More Robust.Devices made from PDMS suffer from leaching and permeability which preclude certain applications and ultimately lead to less effective focusing.
  • Increased Efficiency. New design parameters based on couple-resonator theory have allowed for increased energy transfer from transducer to fluid.
  • Tunable Nodes.Novel device geometries incorporating a virtually transparent wall allow for adjustable positioning of pressure node locations.
Potential Applications

Primary market applications of this device could include liquid biopsy for circulating tumor cells, blood washing in major surgery, platelet separation, cell sample processing for flow cytometry, and discovery (e.g. phage and biomarker selection).

Development Status

LLNL is seeking patent protection on this invention which builds on our exiting patent portfolio for our microfluidic ultrasonic particle separators.

U.S. Patent 8,727,129 Microfluidic Ultrasonic Particle Separators with Engineered Node Locations and Geometries U.S. Patent 8,991,614

U.S. Patent Application 14/659825 (pending)

Reference Number
29915