Zhichao Ma

Highly Localized Acoustic Streaming and Size-Selective Submicrometer Particle Concentration Using High Frequency Microscale Focused Acoustic Fields

Concentration and separation of particles and biological specimens are fundamental functions of micro/nanofluidic systems. Acoustic streaming is an effective and biocompatible way to create rapid microscale fluid motion and induce particle capture, though the >100 MHz frequencies required to directly generate acoustic body forces on the microscale have traditionally been difficult to generate and localize in a way that is amenable to efficient generation of streaming. Moreover, acoustic, hydrodynamic, and electrical forces as typically applied have difficulty manipulating specimens in the submicrometer regime. In this work, we introduce highly focused traveling surface acoustic waves (SAW) at high frequencies between 193 and 636 MHz for efficient and highly localized production of acoustic streaming vortices on microfluidic length scales. Concentration occurs via a novel mechanism, whereby the combined acoustic radiation and streaming field results in size-selective aggregation in fluid streamlines in the vicinity of a high-amplitude acoustic beam, as opposed to previous acoustic radiation induced particle concentration where objects typically migrate toward minimum pressure locations. Though the acoustic streaming is induced by a traveling wave, we are able to manipulate particles an order of magnitude smaller than possible using the traveling wave force alone. We experimentally and theoretically examine the range of particle sizes that can be captured in fluid streamlines using this technique, with rapid particle concentration demonstrated down to 300 nm diameters. We also demonstrate that locations of trapping and concentration are size-dependent, which is attributed to the combined effects of the acoustic streaming and acoustic forces.

Detachable Acoustofluidic System for Particle Separation via a Traveling Surface Acoustic Wave

Components in biomedical analysis tools that have direct contact with biological samples, especially biohazardous materials, are ideally discarded after use to prevent cross-contamination. However, a conventional acoustofluidic device is typically a monolithic integration that permanently bonds acoustic transducers with microfluidic channels, increasing processing costs in single-use platforms. In this study, we demonstrate a detachable acoustofluidic system comprised of a disposable channel device and a reusable acoustic transducer for noncontact continuous particle separation via a traveling surface acoustic wave (TSAW). The channel device can be placed onto the SAW transducer with a high alignment tolerance to simplify operation, is made entirely of polydimethylsiloxane (PDMS), and does not require any additional coupling agent. A microstructured pillar is used to couple acoustic waves into the fluid channel for noncontact particle manipulation. We demonstrate the separation of 10 and 15 μm particles at high separation efficiency above 98% in a 49.5 MHz TSAW using the developed detachable acoustofluidic system. Its disposability and ease of assembly should enable broad use of noncontact, disposable particle manipulation techniques in practical biomedical applications related to sample preparation.

Acoustic tweezers via sub-time-of-flight regime surface acoustic waves.

Researchers use pulsed excitation to generate localized 2D acoustic tweezers for spatially selective microfluidic patterning. Micrometer-scale acoustic waves are highly useful for refined optomechanical and acoustofluidic manipulation, where these fields are spatially localized along the transducer aperture but not along the acoustic propagation direction. In the case of acoustic tweezers, such a conventional acoustic standing wave results in particle and cell patterning across the entire width of a microfluidic channel, preventing selective trapping. We demonstrate the use of nanosecond-scale pulsed surface acoustic waves (SAWs) with a pulse period that is less than the time of flight between opposing transducers to generate localized time-averaged patterning regions while using conventional electrode structures. These nodal positions can be readily and arbitrarily positioned in two dimensions and within the patterning region itself through the imposition of pulse delays, frequency modulation, and phase shifts. This straightforward concept adds new spatial dimensions to which acoustic fields can be localized in SAW applications in a manner analogous to optical tweezers, including spatially selective acoustic tweezers and optical waveguides.

Continuous micro-vortex-based nanoparticle manipulation via focused surface acoustic waves

Despite increasing demand in the manipulation of nanoscale objects for next generation biological and industrial processes, there is a lack of methods for reliable separation, concentration and purification of nanoscale objects. Acoustic methods have proven their utility in contactless manipulation of microscale objects mainly relying on the acoustic radiation effect, though the influence of acoustic streaming has typically prevented manipulation at smaller length scales. In this work, however, we explicitly take advantage of the strong acoustic streaming in the vicinity of a highly focused, high frequency surface acoustic wave (SAW) beam emanating from a series of focused 6 μm substrate wavelength interdigital transducers patterned on a piezoelectric lithium niobate substrate and actuated with a 633 MHz sinusoidal signal. This streaming field serves to focus fluid streamlines such that incoming particles interact with the acoustic field similarly regardless of their initial starting positions, and results in particle displacements that would not be possible with a travelling acoustic wave force alone. This streaming-induced manipulation of nanoscale particles is maximized with the formation of micro-vortices that extend the width of the microfluidic channel even with the imposition of a lateral flow, occurring when the streaming-induced flow velocities are an order of magnitude larger than the lateral one. We make use of this acoustic streaming to demonstrate the continuous and differential focusing of 100 nm, 300 nm and 500 nm particles.

Self-Aligned Interdigitated Transducers for Acoustofluidics

The surface acoustic wave (SAW) is effective for the manipulation of fluids and particles at microscale. The current approach of integrating interdigitated transducers (IDTs) for SAW generation into microfluidic channels involves complex and laborious microfabrication steps. These steps often require full access to clean room facilities and hours to align the transducers to the precise location. This work presents an affordable and innovative method for fabricating SAW-based microfluidic devices without the need for clean room facilities and alignment. The IDTs and microfluidic channels are fabricated using the same process and thus are precisely self-aligned in accordance with the device design. With the use of the developed fabrication approach, a few types of different SAW-based microfluidic devices have been fabricated and demonstrated for particle separation and active droplet generation.

Sheathless inertial cell focusing and sorting with serial reverse wavy channel structures

Inertial microfluidics utilizing passive hydrodynamic forces has been attracting significant attention in the field of precise microscale manipulation owing to its low cost, simplicity and high throughput. In this paper, we present a novel channel design with a series of reverse wavy channel structures for sheathless inertial particle focusing and cell sorting. A single wavy channel unit consists of four semicircular segments, which produce periodically reversed Dean secondary flow along the cross-section of the channel. The balance between the inertial lift force and the Dean drag force results in deterministic equilibrium focusing positions, which also depends on the size of the flow-through particles and cells. Six sizes of fluorescent microspheres (15, 10, 7, 5, 3 and 1 μm) were used to study the size-dependent inertial focusing behavior. Our novel design with sharp-turning subunits could effectively focus particles as small as 3 μm, the average size of platelets, enabling the sorting of cancer cells from whole blood without the use of sheath flows. Utilizing an optimized channel design, we demonstrated the size-based sorting of MCF-7 breast cancer cells spiked in diluted whole blood samples without using sheath flows. A single sorting process was able to recover 89.72% of MCF-7 cells from the original mixture and enrich MCF-7 cells from an original purity of 5.3% to 68.9% with excellent cell viability.Cell sorting: Effective separation in wavy channelsA technique for sorting tiny objects based on their size as they flow through narrow channels offers a simple system that could be used to separate cells and smaller bodies such as blood platelets. Separating different cells and other components of biological fluids is a vital aspect of medical research toward the development of new therapies. All existing methods have limitations, and improved techniques are eagerly sought. Ye Ai and colleagues at Singapore University of Technology and Design developed and tested a simple method based on the forces particles experience as they flow through channels with semi-circular sections linked in repeatedly reversing directions. The researchers demonstrated the general performance of their technique using fluorescent microspheres. They then successfully separated cancer cells from blood. The method could allow fast and efficient cell-sorting in many biomedical applications.

Precise Cell Manipulation using High Frequency Surface Acoustic Waves

Precise manipulation of particles and biological cells is an essential process in various biomedical research fields, industrial and clinical applications. Among various force fields applied for microfluidic cell manipulation, acoustic waves have superior propagating properties in solids and fluids, which can readily enable non-contact cell manipulation in long operating distances. In addition, acoustic fields are advantageous to high power laser beams for non-contact optical tweezing in terms of biocompatibility, throughput and setup simplicity. Exploiting acoustic waves for fluid and cell manipulation in microfluidics has led to a newly emerging research area, acoustofluidics. In this presentation, I will talk about particle and cell manipulation in microfluidics using high frequency surface acoustic waves (SAW). In particular, I will discuss a unique design of a focused IDT (FIDT) structure, which is able to generate a highly localized SAW field on the order of 20 µm wide. This highly focused acoustic beam has an effective manipulation area size that is comparable to individual micron-sized particles. Here, I demonstrate the use of this highly localized SAW field for single cell level sorting using sub-millisecond pulses and selective capture of cells.

Fluorescence activated cell sorting via focused traveling surface acoustic waves (FTSAWs)

Fluorescence Activated Cell Sorting (FACS) is an essential technique widely used in biomedical analyses. Microfluidics, benefiting at its low power and sample consumption, has enabled miniaturization of the existing bulk FACS equipment into cost-effective and portable devices. However, these devices still have limited efficiency and biocompatibility whose actuation is based on dielectrophoresis, optical tweezers, and gas valve. Acoustophoresis, the migration of particles in acoustic field, has recently emerged as a promising method to manipulate suspended particles in microscale, thanks to the rapid response and good biocompatibility. However, limited by the wide aperture of the acoustic field, cell encapsulation in ~100s μm of droplets is one of the necessary procedures in the demonstrated acoustophoresis based FACS system to ensure sort single cell at each actuation, increasing the complexity of the system. In present work, a FACS system actuated by focused traveling surface acoustic waves has been deve...