Acoustic tweezers for the life sciences

Abstract

Acoustic tweezers are a versatile set of tools that use sound waves to manipulate bioparticles ranging from nanometer-sized extracellular vesicles to millimeter-sized multicellular organisms. Over the past several decades, the capabilities of acoustic tweezers have expanded from simplistic particle trapping to precise rotation and translation of cells and organisms in three dimensions. Recent advances have led to reconfigured acoustic tweezers that are capable of separating, enriching, and patterning bioparticles in complex solutions. Here, we review the history and fundamentals of acoustic-tweezer technology and summarize recent breakthroughs.

Fig. 1 |. Illustrations of various acoustic-tweezer technologies.

a, A typical BAW-based standing-wave tweezer device. The number of pressure nodes and antinodes inside the channel is determined by adjusting the applied acoustic wave frequency with respect to the distance between the matching layer and the reflection layer. b, SAW-based standing-wave tweezers use IDTs to generate mechanical waves. Four sets of IDTs are used to generate a 2D pressure-node field that traps and patterns particles. c, Active traveling-wave tweezers with a transducer array to manipulate particles. By controlling the relative phase of the acoustic wave from each transducer, flexible pressure nodes can be formed to achieve dynamic patterning. d, Passive traveling-wave tweezers with a single transducer to achieve complex acoustic distributions and control over particles. e, Acoustic-streaming tweezers use oscillating microbubbles inside a microfluidic channel to generate out-of-plane acoustic microstreaming flows. f, Solid-structure-based acoustic-streaming tweezers generate a directional fluid flow under acoustic excitation.

Fig. 2 |. Acoustic manipulation of various sample sizes and types.

a, Two pairs of IDTs are configured to generate a planar standing-wave field. The inset demonstrates the path of a single particle in 3D. b, Numerical simulation results show the mapping of the acoustic field around a single particle that demonstrates the operating principle for 3D manipulation with standing-wave tweezers. c, Acoustically driven microbubbles are used to trap and rotationally manipulate C. elegans under a fluorescence microscope to visualize ALA-neuron dendrites that are overlapping in the dorsoventral view. A, anterior; P, posterior; L, left; R, right. Scale bar, 40 μm. d, Two HEK 293T cells are manipulated toward each other and brought into contact for intercellular-communication applications. Scale bar, 20 μm. a, b, and d are reprinted with permission from refs ^,, respectively, National Academy of Sciences. c is reprinted with permission from ref. , Springer Nature.

Fig. 3 |. Acoustic manipulation of single particles and droplets.

a, A polystyrene particle is levitated and moved in 3D by controlling the phase difference in active traveling-wave tweezers. Scale bar, 20 mm. b, Acoustic-based droplet manipulation in an open system is demonstrated. Two droplets that are pipetted from the holes are transported, mixed, and ejected into a 24-well plate. a and b are reprinted with permission from refs ^,, respectively, Springer Nature.

Fig. 4 |. Acoustic isolation of exosomes from whole blood.

a, A schematic depiction of exosome isolation via standing-wave tweezers. Red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs) are filtered by the cell-removal module, and then subgroups of extracellular vesicles (ABs, apoptotic bodies; MVs, microvesicles; EXOs, exosomes) are separated by the exosome-isolation module. b,c, Images were taken under a microscope at the cell-removal module (b) and the exosome-isolation module (c) of the device. b, RBCs, WBCs, and PLTs are shown to be pushed to the cell-waste outlet in the cell-removal module. c, Exosomes are separated from microvesicles and apoptotic bodies at the exosome-isolation module. Scale bars, 500 μm. Reprinted with permission from ref. , National Academy of Sciences.

Fig. 5 |. Acoustic-based 2D single-cell patterning.

a, Schematic depiction of a single-cell-patterning device with one cell per pressure node. b, 6.1-μm polystyrene particles suspended in water are introduced inside a microchannel. PDMS, polydimethylsiloxane. c, After the acoustic field with a frequency of 171 MHz is turned on, particles are patterned as one particle per acoustic well. Scale bar, 100 μm. d, A sample of red blood cells patterned in 2D easily revealed cells infected with the green fluorescent protein-expressing malarial parasite P. falciparum. Scale bars, 40 μm. Reprinted with permission from ref. , Springer Nature.