UC San Diego

Acoustic actuation of fluids at small scales may finally enable a comprehensive lab-on-a-chip revolution in microfluidics, overcoming long-standing difficulties in fluid and particle manipulation on-chip. In the introductory chapter, we examine the fundamentals of piezoelectricity, piezoelectric materials, and transducers; revisit the basics of acoustofluidics; and give the reader a detailed look at recent technological advances and current scientific discussions in the discipline. Recent achievements are placed in the context of classic reports for the actuation of fluid and particles via acoustic waves, both within sessile drops and closed channels. Other aspects of micro/nano acoustofluidics are examined: atomization, translation, mixing, jetting, and particle manipulation in the context of sessile drops and fluid mixing and pumping,particle manipulation, and formation of droplets in the context of closed channels, plus the most recent results at the nanoscale. These achievements will enable applications across the disciplines of chemistry, biology, medicine, energy, manufacturing, and we suspect a number of others yet unimagined. Basic design concepts and illustrative applications are highlighted in each section, with an emphasis on lab-on-a-chip applications. This paper also presents a review of waveguides on lithium niobate for surface acoustic waves (SAW), including in particular the classic literature on the topic with the intent of renewing interest in them in the context of potential applications in the burgeoning discipline of micro to nano-scale acoustofluidics. From the fundamentals of the piezoelectric effect we describe interdigital electrodes and how they generate acoustic waves, consider focusing interdigital electrodes as a simple means of laterally confining the acoustic energy propagating across a substrate, and then quickly move to waveguiding structures that provide confinement by defining either a region of slow wave velocity or a physically isolated structure. The ability to steer acoustic waves using these waveguides is considered. The many analytical, computational, and experimental tools devised by past investigators to design them are discussed in detail, as are the relative advantages and disadvantages of the waveguide designs considered over the years. Two fabrication techniques, lift-off and wet etching, are described in producing interdigital electrode transducers upon a piezoelectric substrate, lithium niobate, widely used to generate SAW now finding broad utility in micro to nanoscale fluidics. We explicitly demonstrate the two methods of fabricating SAW devices on lithium niobate, step-by-step. Representative results for the electrode pattern deposited on the substrate as well as the performance of SAW generated on the surface are displayed in detail. Fabrication tricks and troubleshooting are covered as well. This procedure offers a practical protocol for high frequency SAW device fabrication and integration for future microfluidics applications. Three-dimensional cell agglomerates are broadly useful in tissue engineering and drug testing. We report a well-free method to form large (1-mm) multicellular clusters using 100-MHz SAW without direct contact with the media or cells. A fluid couplant is used to transform the SAW into acoustic streaming in the cell-laden media held in a petri dish. The couplant transmits longitudinal sound waves, forming a Lamb wave in the petri dish that, in turn, produces longitudinal sound in the media. Due to recirculation, human embryonic kidney (HEK293) cells in the dish are carried to the center of the coupling location, forming a cluster in less than 10 min. A few minutes later, these clusters may then be translated and merged to form large agglomerations, and even repeatedly folded to produce a roughly spherical shape of over 1 mm in diameter for incubation|without damaging the existing intercellular bonds. Calcium ion signaling through these clusters and confocal images of multiprotein junctional complexes suggest a continuous tissue construct: intercellular communication. They may be formed at will, and the method is feasibly useful for formation of numerous agglomerates in a single petri dish.