Three-dimensional manipulation of single cells using surface acoustic waves

Abstract

The ability of surface acoustic waves to trap and manipulate micrometer-scale particles and biological cells has led to many applications involving "acoustic tweezers" in biology, chemistry, engineering, and medicine. Here, we present 3D acoustic tweezers, which use surface acoustic waves to create 3D trapping nodes for the capture and manipulation of microparticles and cells along three mutually orthogonal axes. In this method, we use standing-wave phase shifts to move particles or cells in-plane, whereas the amplitude of acoustic vibrations is used to control particle motion along an orthogonal plane. We demonstrate, through controlled experiments guided by simulations, how acoustic vibrations result in micromanipulations in a microfluidic chamber by invoking physical principles that underlie the formation and regulation of complex, volumetric trapping nodes of particles and biological cells. We further show how 3D acoustic tweezers can be used to pick up, translate, and print single cells and cell assemblies to create 2D and 3D structures in a precise, noninvasive, label-free, and contact-free manner.3D acoustic tweezers | cell printing | 3D cell manipulation | cell assembly | 3D particle manipulationT he ability to precisely manipulate living cells in three dimensions, one cell at a time, offers many possible applications in regenerative medicine, tissue engineering, neuroscience, and biophysics (1-3). However, current bioprinting methods are generally hampered by the need to reconstruct and mimic 3D cellto-cell communications and cell-environment interactions. Because of this constraint, bioprinting requires accurate reproduction of multicellular architecture (4, 5). Several approaches have been developed to produce complex cell patterns, clusters, assembled arrays, and even tissue structures. These approaches use many disparate technologies which include optics, magnetic and electrical fields, injection printing, physical or geometric constraints, or surface engineering (6-11). However, there is currently a paucity of a single method that can facilitate the formation of complex multicellular structures with high precision, high versatility, multiple dimensionality, and single-cell resolution, while maintaining cell viability, integrity, and function. As a result, there is a critical need to develop new methods that seek to overcome these limitations."Acoustic tweezers," which manipulate biological specimens using sound waves, offer several unique advantages (12, 13) in comparison with other techniques. First, the acoustic tweezers technology is the only active cell-manipulation method using gentle mechanical vibrations that do not alter cell characteristics. Acoustic vibrations create a pressure gradient in the medium to move suspended microobjects and cells, thereby resulting in a contaminationfree, contact-less, and label-free method for cell manipulation. Sound waves are preferred for cell manipulation for the following reasons: (i) cells maintain their native state (e.g., shape, size, reflective index,...

Patterning and manipulating microparticles into a three-dimensional matrix using standing surface acoustic waves

“…Similar to reports in the literature, 7,8,13,14 when the two orthogonal pairs of IDTs are supplied with the signal simultaneously, the microparticles aggregate at the nodes to form 2D horizontal patterns. Because the intersection of two orthogonal pressure lines forms a pressure node, the microparticles form 2D matrix patterns under the bidirectional acoustic radiation force.…”

“…Precise control of microparticles on the horizontal (xy) plane is easily realized and has been reported variously. 8,14 Herein, we have demonstrated that the vertical positions of microparticles can be controlled precisely and manipulated by adjusting the input power.…”

“…There was a report of trapping microparticles into nodes using "3D acoustic tweezers" which was created by locating two pairs of IDTs perpendicularly to each other. 8 These trapping nodes could be translated horizontally by changing the relative phases of the pairs of opposing IDTs. Thus, the microparticles trapped in the nodes were also transported accordingly.…”

Observation of Metal Nanoparticles for Acoustic Manipulation

“…As a noninvasive and noncontact manipulation method, acoustic trapping has the advantage that it is able to simply levitate many kinds of objects from small living animal to bacteria 15, 16, 17, 18, 19, 20, 21. More importantly, the penetration of sound wave is much deeper than light in nontransparent media.…”

“…More importantly, the penetration of sound wave is much deeper than light in nontransparent media. In addition, acoustic trapping has been demonstrated the ability to restrict objects on the scale of large populations 19, 20. Techniques to achieve this goal are usually based on acoustic radiation force under a certain type of acoustic field, especially using counter‐propagating waves to set up standing wave nodes to trap the particles 15, 17, 21, 22, 23, 24.…”