Acoustic focusing with engineered node locations for high-performance microfluidic particle separation

Abstract

Acoustofluidic devices for manipulating microparticles in fluids are appealing for biological sample processing due to their gentle and high-speed capability of sorting cell-scale objects. Such devices are generally limited to moving particles toward locations at integer fractions of the fluid channel width (1/2, 1/4, 1/6, etc.). In this work, we introduce a unique approach to acoustophoretic device design that overcomes this constraint, allowing us to design the particle focusing location anywhere within the microchannel. This is achieved by fabricating a second fluid channel in parallel with the sample channel, separated from it by a thin silicon wall. The fluids in both channels participate to create the ultrasound resonance, while only one channel processes the sample, thus de-coupling the fluidic and acoustic boundaries. The wall placement and the relative widths of the adjacent channels define the particle focusing location. We investigate the operating characteristics of a range of these devices to determine the configurations that enable effective particle focusing and separation. The results show that a sufficiently thin wall negligibly affects focusing efficiency and location compared to a single channel without a wall, validating the success of this design approach without compromising separation performance. Using these principles to design and fabricate an optimized device configuration, we demonstrate high-efficiency focusing of microspheres, as well as separation of cell-free viruses from mammalian cells. These "transparent wall" acoustic devices are capable of over 90% extraction efficiency with 10 μm microspheres at 450 μL min(-1), and of separating cells (98% purity), from viral particles (70% purity) at 100 μL min(-1).

Microfluidic cell sorting: a review of the advances in the separation of cells from debulking to rare cell isolation

“…created an H-filter device that can form bulk acoustic standing waves with the node offset from the center of a microfluidic channel for a new method of acoustic cell sorting. 109 …”

Microparticle Response to Two-Dimensional Streaming Flows in Rectangular Chambers Undergoing Low-Frequency Horizontal Vibrations

“…The acoustic radiation force causes particles to migrate (over thousands of cycles) towards the pressure nodes or antinodes, depending on their acoustic contrast factor. The acoustic radiation force has been analytically formulated [5,6] and, subsequently, has been used to manipulate particles for applications in flowing [7][8][9][10] and in stationary fluid volumes. In closed microfluidic systems, it has been used to collect particles in lines [11,12], 2D arrays [13,14], and 3D cages [15] and manipulate particles in the form of acoustic tweezers, through phase control [16] and mode switching [17,18].…”

Spatial tuning of acoustofluidic pressure nodes by altering net sonic velocity enables high-throughput, efficient cell sorting

“…1,2 Acoustophoresis has been adapted for a wide range of applications that require well-controlled conditions provided by laminar flow, such as sorting or synchronizing cells, 3 manipulating single cells, 4 enriching circulating tumor cells, 5 and separating cells from virus. 6 …”

“…1). Channels are anisotropically deep reactive–ion etched 200 μm deep on <100> silicon wafers; 6 the widths of the main and echo/bypass channels are 300 and 597 μm, respectively, and they are separated by a thin 10-μm silicon wall. After anodically bonding borosilicate glass to seal the channel, this wall creates a physical barrier that prevents media from mixing between different channels, but allows ultrasonic waves to pass through.…”