Xiaoyun Ding

On-chip manipulation of single microparticles, cells, and organisms using surface acoustic waves

Techniques that can dexterously manipulate single particles, cells, and organisms are invaluable for many applications in biology, chemistry, engineering, and physics. Here, we demonstrate standing surface acoustic wave based “acoustic tweezers” that can trap and manipulate single microparticles, cells, and entire organisms (i.e., Caenorhabditis elegans) in a single-layer microfluidic chip. Our acoustic tweezers utilize the wide resonance band of chirped interdigital transducers to achieve real-time control of a standing surface acoustic wave field, which enables flexible manipulation of most known microparticles. The power density required by our acoustic device is significantly lower than its optical counterparts (10,000,000 times less than optical tweezers and 100 times less than optoelectronic tweezers), which renders the technique more biocompatible and amenable to miniaturization. Cell-viability tests were conducted to verify the tweezers’ compatibility with biological objects. With its advantages in biocompatibility, miniaturization, and versatility, the acoustic tweezers presented here will become a powerful tool for many disciplines of science and engineering.

Surface acoustic wave microfluidics

The recent introduction of surface acoustic wave (SAW) technology onto lab-on-a-chip platforms has opened a new frontier in microfluidics. The advantages provided by such SAW microfluidics are numerous: simple fabrication, high biocompatibility, fast fluid actuation, versatility, compact and inexpensive devices and accessories, contact-free particle manipulation, and compatibility with other microfluidic components. We believe that these advantages enable SAW microfluidics to play a significant role in a variety of applications in biology, chemistry, engineering and medicine. In this review article, we discuss the theory underpinning SAWs and their interactions with particles and the contacting fluids in which they are suspended. We then review the SAW-enabled microfluidic devices demonstrated to date, starting with devices that accomplish fluid mixing and transport through the use of travelling SAW; we follow that by reviewing the more recent innovations achieved with standing SAW that enable such actions as particle/cell focusing, sorting and patterning. Finally, we look forward and appraise where the discipline of SAW microfluidics could go next.

Cell separation using tilted-angle standing surface acoustic waves

Significance We have developed a unique approach for the separation of particles and biological cells through standing surface acoustic waves oriented at an optimum angle to the fluid flow direction in a microfluidic device. This experimental setup, optimized by systematic analyses, has been used to demonstrate effective separation based on size, compressibility, and mechanical properties of particles and cells. The potential of this method for biological–biomedical applications was demonstrated through the example of isolating MCF-7 breast cancer cells from white blood cells. The method offers a possible route for label-free particle or cell separation for many applications in research, disease diagnosis, and drug-efficacy assessment. 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.

Three-dimensional continuous particle focusing in a microfluidic channel via standing surface acoustic waves (SSAW)†

Three-dimensional (3D) continuous microparticle focusing has been achieved in a single-layer polydimethylsiloxane (PDMS) microfluidic channel using a standing surface acoustic wave (SSAW). The SSAW was generated by the interference of two identical surface acoustic waves (SAWs) created by two parallel interdigital transducers (IDTs) on a piezoelectric substrate with a microchannel precisely bonded between them. To understand the working principle of the SSAW-based 3D focusing and investigate the position of the focal point, we computed longitudinal waves, generated by the SAWs and radiated into the fluid media from opposite sides of the microchannel, and the resultant pressure and velocity fields due to the interference and reflection of the longitudinal waves. Simulation results predict the existence of a focusing point which is in good agreement with our experimental observations. Compared with other 3D focusing techniques, this method is non-invasive, robust, energy-efficient, easy to implement, and applicable to nearly all types of microparticles.

In vitro and ex vivo strategies for intracellular delivery

Intracellular delivery of materials has become a critical component of genome-editing approaches, ex vivo cell-based therapies, and a diversity of fundamental research applications. Limitations of current technologies motivate development of next-generation systems that can deliver a broad variety of cargo to diverse cell types. Here we review in vitro and ex vivo intracellular delivery approaches with a focus on mechanisms, challenges and opportunities. In particular, we emphasize membrane-disruption-based delivery methods and the transformative role of nanotechnology, microfluidics and laboratory-on-chip technology in advancing the field.

Standing surface acoustic wave (SSAW) based multichannel cell sorting

We introduce a novel microfluidic device for cell sorting in continuous flow using tunable standing surface acoustic waves. This method allows individual cells to be precisely directed into five different outlet channels in a single step. It is versatile, simple, label-free, non-invasive, and highly controllable.

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).

Tunable nanowire patterning using standing surface acoustic waves.

Patterning of nanowires in a controllable, tunable manner is important for the fabrication of functional nanodevices. Here we present a simple approach for tunable nanowire patterning using standing surface acoustic waves (SSAW). This technique allows for the construction of large-scale nanowire arrays with well-controlled patterning geometry and spacing within 5 s. In this approach, SSAWs were generated by interdigital transducers, which induced a periodic alternating current (ac) electric field on the piezoelectric substrate and consequently patterned metallic nanowires in suspension. The patterns could be deposited onto the substrate after the liquid evaporated. By controlling the distribution of the SSAW field, metallic nanowires were assembled into different patterns including parallel and perpendicular arrays. The spacing of the nanowire arrays could be tuned by controlling the frequency of the surface acoustic waves. Additionally, we observed 3D spark-shaped nanowire patterns in the SSAW field. The SSAW-based nanowire-patterning technique presented here possesses several advantages over alternative patterning approaches, including high versatility, tunability, and efficiency, making it promising for device applications.

Tunable patterning of microparticles and cells using standing surface acoustic waves

We have developed an acoustic-based tunable patterning technique by which microparticles or cells can be arranged into reconfigurable patterns in microfluidic channels. In our approach, we use pairs of slanted-finger interdigital transducers (SFITs) to generate a tunable standing surface acoustic wave field, which in turn patterns microparticles or cells in one- or two-dimensional arrays inside the microfluidic channels--all without the assistance of fluidic flow. By tuning the frequency of the input signal applied to the SFITs, we have shown that the cell pattern can be controlled with tunability of up to 72%. This acoustic-based tunable patterning technique has the advantages of wide tunability, non-invasiveness, and ease of integration to lab-on-a-chip systems, and shall be valuable in many biological and colloidal studies.

Surface acoustic wave driven light shutters using polymer-dispersed liquid crystals.

displays, [ 3 ] microlenses, [ 4 , 5 ] lasers, [ 6 , 7 ] and data storage, [ 8 ] due to their excellent electro-optical properties. PDLC fi lms can be prepared between two conductive, transparent substrates using methods such as encapsulation, thermally induced phase separation, solvent-induced phase separation, and polymerizationinduced phase separation. [ 9 ] Within a PDLC fi lm, liquid crystals (LCs) are generally trapped in a transparent polymer medium, thus forming micrometer-scale LC droplets. The random dispersion of LC droplets in the polymer matrix causes a strong scattering of light due to the signifi cant refractive index mismatch between the two materials; therefore, a PDLC fi lm is naturally opaque. Based on laser interference holography, various periodic structures such as gratings [ 10–12 ] and photonic crystals, [ 13 , 14 ] can be also introduced inside the fi lm, coined as holographic PDLCs (HPDLCs). [ 15 ] The application of an electric fi eld can re-orientate the LC molecules inside a droplet, thus modulating the refractive index difference between the polymer matrix and the LC. A complete refractive index match between the two materials can be achieved by tuning the LCs to a specifi c orientation. In such a way, the PDLC fi lm can be switched from opaque to transparent. The switching properties of PDLCs are infl uenced by many variables including the size and shape of the LC droplets, [ 16 , 17 ] and molecular interactions between the LCs and polymer matrix. [ 18 , 19 ]