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Acoustofluidics for biomedical applications

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Abstract

Acoustofluidic technologies utilize acoustic waves to manipulate fluids and particles within fluids, all in a contact-free and biocompatible manner. Over the past decade, acoustofluidic technologies have enabled new capabilities in biomedical applications ranging from the precise patterning of heterogeneous cells for tissue engineering to the automated isolation of extracellular vesicles from biofluids for rapid, point-of-care diagnostics. In this Primer, we explain the underlying physical principles governing the design and operation of acoustofluidic technologies and describe the various implementations that have been developed for biomedical applications. We aim to demystify the rapidly growing field of acoustofluidics and provide a unified perspective that will allow end users to choose the acoustofluidic technology that is best suited for their research needs. The experimental set-ups for each type of acoustofluidic device are discussed along with their advantages and limitations. In addition, we review typical types of data that are obtained from acoustofluidic experiments and describe how to model different forces acting on particles within an acoustofluidic device. We also discuss data reproducibility and the need to establish standards for the deposition of data sets within the field. Finally, we provide our perspective on how to optimize device performance and discuss areas of future development.

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Fig. 1: Typical configurations of acoustofluidic devices.
Fig. 2: Representative acoustofluidics results based on acoustic radiation forces.
Fig. 3: Representative acoustofluidics results based on acoustic streaming.
Fig. 4: Acoustofluidics for single-cell analysis.
Fig. 5: Acoustofluidics for point-of-care diagnostics.
Fig. 6: Acoustofluidics for the automation of workflows in biomedical laboratories.
Fig. 7: Acoustofluidics for tissue engineering.

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Acknowledgements

The authors acknowledge support from the National Institutes of Health (NIH) (U18TR003778, R01GM135486, UH3TR002978, R01GM141055, R01GM132603, R01HD103727 and R01NS115591), National Science Foundation (NSF) (ECCS-1807601 and ECCS-1542148), National Natural Science Foundation of China (11974372) (to F.C.) and W.M. Keck Foundation. They thank S. Yang, S. P. Zhang, R. Zhong and L. Zhang for helpful discussion.

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Authors and Affiliations

  1. Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA

    Joseph Rufo & Tony Jun Huang

  2. Paul C. Lauterbur Research Centre for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China

    Feiyan Cai

  3. Center for Medical Device Engineering and Biomechanics, Department of Mechanical and Aerospace Engineering, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, USA

    James Friend

  4. Department of Surgery, School of Medicine, University of California San Diego, La Jolla, CA, USA

    James Friend

  5. Department of Applied Physics, Royal Institute of Technology, Stockholm, Sweden

    Martin Wiklund

Authors
  1. Joseph Rufo
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  2. Feiyan Cai
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  3. James Friend
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  4. Martin Wiklund
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  5. Tony Jun Huang
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Contributions

Introduction (T.J.H., J.R., F.C. and J.F.); Experimentation (J.F., F.C., J.R. and T.J.H.); Results (F.C., J.F., J.R. and T.J.H.); Applications (T.J.H. and J.R.); Reproducibility and data deposition (M.W., J.R. and T.J.H.); Limitations and optimizations (M.W., J.R. and T.J.H.); Outlook (T.J.H., J.R. and M.W.); Overview of the Primer (T.J.H.).

Corresponding authors

Correspondence to Feiyan Cai, James Friend, Martin Wiklund or Tony Jun Huang.

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Competing interests

T.J.H. has co-founded a start-up company, Ascent Bio-Nano Technologies Inc., to commercialize technologies involving acoustofluidics and acoustic tweezers. J.F. is a founding partner of Sonocharge Inc., commercializing acoustically driven rechargeable battery enhancement technology, and ARNAsystems Inc., commercializing rapid acoustofluidic diagnostic devices. J.R., F.C. and M.W. declare no competing interests.

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Nature Reviews Methods Primers thanks Ye Ai, Helen Mulvana and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Inviscid fluid

A fluid that has a viscosity of zero.

Rayleigh particle

A particle that has a radius that is much smaller than the acoustic wavelength.

Standing wave

A stationary wave formed by the superposition of counterpropagating travelling waves, which are commonly formed by the use of opposing transducers or reflective surfaces.

Zero mean mass flux

The absence of mass flow.

Zero Lagrangian mean

The Lagrangian specification of fluid flow states that the observer follows individual fluid parcels through time.

Eulerian mean

The Eulerian specification of fluid flow states that the observer follows a specific location in space through which the fluid flows as time passes.

Q factor

Shorthand for the quality factor, a parameter that quantifies the damping at each resonance frequency.

Time-reversal principle

A signal processing technique that can be used to focus acoustic waves to a specific location.

Rayleigh (surface) wave

A flexural wave isolated to a surface. Typically generated for acoustofluidics using an interdigital electrode deposited upon a piezoelectric substrate.

Lamb wave

A flexural wave in a structure that has a wavelength at or less than two times the thickness of the structure. Typically appears in surface acoustic wave (SAW) devices in the piezoelectric media when the resonance frequency is too low to isolate the wave to the surface.

Pressure nodes

Minimum pressure locations.

Pressure antinodes

Maximum pressure locations.

Mie particles

Particles of about the same size as the acoustic wavelength.

Acoustic levitation

The use of the acoustic radiation force to counteract gravity and suspend a particle in air.

Dynamic gradient field

A field in which the acoustic gradient force changes with time.

Iso-acoustic point

When particles or cells flow through a liquid that has a gradient in its acoustic impedance, the iso-acoustic point represents the location where the acoustic contrast between the particle/cell and the surrounding liquid is zero.

Exosomes

Nanometre-sized extracellular vesicles that contain molecular cargo from their cell of origin.

Acoustic cavitation

The growth and collapse of microbubbles under the influence of an acoustic field in liquids.

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Rufo, J., Cai, F., Friend, J. et al. Acoustofluidics for biomedical applications. Nat Rev Methods Primers 2, 30 (2022). https://doi.org/10.1038/s43586-022-00109-7

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