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Harmonic acoustics for dynamic and selective particle manipulation


Precise and selective manipulation of colloids and biological cells has long been motivated by applications in materials science, physics and the life sciences. Here we introduce our harmonic acoustics for a non-contact, dynamic, selective (HANDS) particle manipulation platform, which enables the reversible assembly of colloidal crystals or cells via the modulation of acoustic trapping positions with subwavelength resolution. We compose Fourier-synthesized harmonic waves to create soft acoustic lattices and colloidal crystals without using surface treatment or modifying their material properties. We have achieved active control of the lattice constant to dynamically modulate the interparticle distance in a high-throughput (>100 pairs), precise, selective and reversible manner. Furthermore, we apply this HANDS platform to quantify the intercellular adhesion forces among various cancer cell lines. Our biocompatible HANDS platform provides a highly versatile particle manipulation method that can handle soft matter and measure the interaction forces between living cells with high sensitivity.

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Fig. 1: Fourier synthesis of harmonic acoustic waves of HANDS to create soft flexible lattices for colloidal crystals or cell–cell pairing and separation.
Fig. 2: Creation of colloid crystal monolayers with cluster and spin dynamics studies via HANDS manipulation.
Fig. 3: HANDS for manipulation of soft matter and living cells for precision quantitative measurements.
Fig. 4: Reversible cell–cell pairings via HANDS for the quantification of intercellular adhesion strength in different cell lines.

Data availability

All the data supporting the findings of this study are available in the article and its Supplementary Information. Further information is available from the corresponding author on reasonable request.

Code availability

The acoustic wave simulations were performed with commercial software MATLAB. Computation details can be made available from the corresponding authors on request.


  1. Li, B., Zhou, D. & Han, Y. Assembly and phase transitions of colloidal crystals. Nat. Rev. Mater. 1, 15011 (2016).

    CAS  Article  Google Scholar 

  2. Hou, J., Li, M. & Song, Y. Recent advances in colloidal photonic crystal sensors: materials, structures and analysis methods. Nano Today 22, 132–144 (2018).

    CAS  Article  Google Scholar 

  3. Lim, M. X., Souslov, A., Vitelli, V. & Jaeger, H. M. Cluster formation by acoustic forces and active fluctuations in levitated granular matter. Nat. Phys. 15, 460–464 (2019).

    CAS  Article  Google Scholar 

  4. Ozcelik, A. et al. Acoustic tweezers for the life sciences. Nat. Methods 15, 1021–1028 (2018).

    CAS  Article  Google Scholar 

  5. Guo, J. et al. Modular assembly of superstructures from polyphenol-functionalized building blocks. Nat. Nanotechnol. 11, 1105–1111 (2016).

    CAS  Article  Google Scholar 

  6. Manoharan, V. N. Colloidal matter: packing, geometry, and entropy. Science 349, 1253751 (2015).

    Article  Google Scholar 

  7. Aubret, A., Youssef, M., Sacanna, S. & Palacci, J. Targeted assembly and synchronization of self-spinning microgears. Nat. Phys. 14, 1114–1118 (2018).

    CAS  Article  Google Scholar 

  8. Liu, B. et al. Switching plastic crystals of colloidal rods with electric fields. Nat. Commun. 5, 3092 (2014).

    Article  Google Scholar 

  9. Demirors, A. F., Pillai, P. P., Kowalczyk, B. & Grzybowski, B. A. Colloidal assembly directed by virtual magnetic moulds. Nature 503, 99–103 (2013).

    Article  Google Scholar 

  10. Yang, D., Ye, S. & Ge, J. Solvent wrapped metastable colloidal crystals: highly mutable colloidal assemblies sensitive to weak external disturbance. J. Am. Chem. Soc. 135, 18370–18376 (2013).

    CAS  Article  Google Scholar 

  11. Ashkin, A., Dziedzic, J. M. & Yamane, T. Optical trapping and manipulation of single cells using infrared laser beams. Nature 330, 769–771 (1987).

    CAS  Article  Google Scholar 

  12. Guo, F. et al. Controlling cell-cell interactions using surface acoustic waves. Proc. Natl Acad. Sci. USA 112, 43–48 (2015).

    CAS  Article  Google Scholar 

  13. Collins, D. J. et al. Two-dimensional single-cell patterning with one cell per well driven by surface acoustic waves. Nat. Commun. 6, 8686 (2015).

    CAS  Article  Google Scholar 

  14. Sitters, G. et al. Acoustic force spectroscopy. Nat. Methods 12, 47–50 (2015).

    CAS  Article  Google Scholar 

  15. Kamsma, D. et al. Single-cell acoustic force spectroscopy: resolving kinetics and strength of T cell adhesion to fibronectin. Cell Rep. 24, 3008–3016 (2018).

    CAS  Article  Google Scholar 

  16. Marzo, A. & Drinkwater, B. W. Holographic acoustic tweezers. Proc. Natl Acad. Sci. USA 116, 84–89 (2019).

    CAS  Article  Google Scholar 

  17. Melde, K., Mark, A. G., Qiu, T. & Fischer, P. Holograms for acoustics. Nature 537, 518–522 (2016).

    CAS  Article  Google Scholar 

  18. Hirayama, R., Plasencia, D. M., Masuda, N. & Subramanian, S. A volumetric display for visual, tactile and audio presentation using acoustic trapping. Nature 575, 320–323 (2019).

    CAS  Article  Google Scholar 

  19. Tian, Z. et al. Wave number–spiral acoustic tweezers for dynamic and reconfigurable manipulation of particles and cells. Sci. Adv. 5, eaau6062 (2019).

    CAS  Article  Google Scholar 

  20. Baudoin, M. et al. Folding a focalized acoustical vortex on a flat holographic transducer: miniaturized selective acoustical tweezers. Sci. Adv. 5, eaav1967 (2019).

    CAS  Article  Google Scholar 

  21. Friend, J. R. & Yeo, L. Y. Microscale acoustofluidics: Microfluidics driven via acoustics and ultrasonics. Rev. Mod. Phys. 83, 647–704 (2011).

    Article  Google Scholar 

  22. Huang, P. H. et al. Acoustofluidic synthesis of particulate nanomaterials. Adv. Sci. 6, 1900913 (2019).

    CAS  Article  Google Scholar 

  23. Gu, Y. et al. Acoustofluidic centrifuge for nanoparticle enrichment and separation. Sci. Adv. 7, eabc0467 (2021).

    CAS  Article  Google Scholar 

  24. Fan, X.-D., Zou, Z. & Zhang, L. Acoustic vortices in inhomogeneous media. Phys. Rev. Res. 1, 032014 (2019).

    CAS  Article  Google Scholar 

  25. Delsing, P. et al. The 2019 surface acoustic waves roadmap. J. Phys. D 52, 353001 (2019).

    CAS  Article  Google Scholar 

  26. Schuetz, M. J. et al. Acoustic traps and lattices for electrons in semiconductors. Phys. Rev. X 7, 041019 (2017).

    Google Scholar 

  27. Schülein, F. J. et al. Fourier synthesis of radiofrequency nanomechanical pulses with different shapes. Nat. Nanotechnol. 10, 512–516 (2015).

    Article  Google Scholar 

  28. Weiß, M. et al. Optomechanical wave mixing by a single quantum dot. Optica 8, 291–300 (2021).

    Article  Google Scholar 

  29. Hosseini, B. H. et al. Immune synapse formation determines interaction forces between T cells and antigen-presenting cells measured by atomic force microscopy. Proc. Natl Acad. Sci. USA 106, 17852–17857 (2009).

    CAS  Article  Google Scholar 

  30. Liu, B., Chen, W., Evavold, B. D. & Zhu, C. Accumulation of dynamic catch bonds between TCR and agonist peptide-MHC triggers T cell signaling. Cell 157, 357–368 (2014).

    CAS  Article  Google Scholar 

  31. Dholakia, K. & Reece, P. Optical micromanipulation takes hold. Nano Today 1, 18–27 (2006).

    Article  Google Scholar 

  32. Feng, Y. et al. Mechanosensing drives acuity of αβ T-cell recognition. Proc. Natl Acad. Sci. USA 114, E8204–E8213 (2017).

    CAS  Google Scholar 

  33. Chen, S. & Lee, L. P. Non-invasive microfluidic gap junction assay. Integr. Biol. 2, 130–138 (2010).

    CAS  Article  Google Scholar 

  34. Glynne-Jones, P., Boltryk, R. J., Harris, N. R., Cranny, A. W. & Hill, M. Mode-switching: a new technique for electronically varying the agglomeration position in an acoustic particle manipulator. Ultrasonics 50, 68–75 (2010).

    CAS  Article  Google Scholar 

  35. Marzo, A., Caleap, M. & Drinkwater, B. W. Acoustic virtual vortices with tunable orbital angular momentum for trapping of mie particles. Phys. Rev. Lett. 120, 044301 (2018).

    CAS  Article  Google Scholar 

  36. Auwerx, J. The human leukemia cell line, THP-1: a multifacetted model for the study of monocyte-macrophage differentiation. Experientia 47, 22–31 (1991).

    CAS  Article  Google Scholar 

  37. Chu, Y. S. et al. Force measurements in E-cadherin-mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42. J. Cell Biol. 167, 1183–1194 (2004).

    CAS  Article  Google Scholar 

  38. Casella, J. F., Flanagan, M. D. & Lin, S. Cytochalasin D inhibits actin polymerization and induces depolymerization of actin filaments formed during platelet shape change. Nature 293, 302–305 (1981).

    CAS  Article  Google Scholar 

  39. Kang, J. H. et al. Noninvasive monitoring of single-cell mechanics by acoustic scattering. Nat. Methods 16, 263–269 (2019).

    CAS  Article  Google Scholar 

  40. Palmer, C. P. et al. Single cell adhesion measuring apparatus (SCAMA): application to cancer cell lines of different metastatic potential and voltage-gated Na+ channel expression. Eur. Biophys. J. 37, 359–368 (2008).

    CAS  Article  Google Scholar 

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We acknowledge support from the Shared Materials Instrumentation Facility at Duke University. We thank S. Suresh, M. Dao, Z. Mao and J. Rich for their critical feedback and helpful discussions. We acknowledge support from the National Institutes of Health (grant numbers R01GM141055 (T.J.H.), R01GM132603 (T.J.H.), U18TR003778 (T.J.H.) and UH3TR002978 (T.J.H.)) and the National Science Foundation (grant numbers ECCS-1807601 (T.J.H.) and CMMI-2104295 (T.J.H.)).

Author information

Authors and Affiliations



S.Y. conceived the idea. S.Y., Z.T., P.L., L.P.L. and T.J.H. designed the research. S.Y. performed the research. Z.W. performed the western blot analysis. S.Y., J.X. and C.C. did the simulation. S.Y., Z.W., Z.T., H.B., C.C., P.L., P.-H.H., M.W., L.P.L. and T.J.H. analysed data. S.Y., P.-H.H., H.B., Z.T. and L.P.L. drew the figures. S.Y., Z.T., Z.W., H.B., P.L., P.-H.H., J.R., J.M., L.P.L. and T.J.H. wrote the paper. S.Y., Z.T., J.R., H.B., P.L., J.M., L.P.L. and T.J.H. revised the paper.

Corresponding authors

Correspondence to Luke P. Lee or Tony Jun Huang.

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Competing interests

T.J.H. has cofounded a start-up company, Ascent Bio-Nano Technologies Inc., to commercialize technologies involving acoustofluidics and acoustic tweezers. The remaining authors declare no competing interests.

Peer review

Peer review information

Nature Materials thanks Hubert Krenner, Adrian Neild and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Notes 1–8, Figs. 1–6 and Table 1.

Supplementary Video 1

Selective and reversible pairing of two cells (U937) by the HANDS platform while keeping neighbouring cells intact.

Supplementary Video 2

Creation of colloidal crystal from a cluster by the HANDS platform.

Supplementary Video 3

Controls of rotational direction and spinning of a colloidal crystal monolayer by the HANDS platform.

Supplementary Video 4

Different crystal configurations of colloidal monolayers with varied spin speeds (with particle number n = 6) by the HANDS platform.

Supplementary Video 5

Reconfiguration of acoustic wells for single-colloid trapping and pairing by the HANDS platform: connected acoustic wells and isolated acoustic wells.

Supplementary Video 6

Demonstration of the repeatable and reversible pairing of single particles by the HANDS platform.

Supplementary Video 7

High-throughput pairing for colloidal particles and cells by the HANDS platform.

Supplementary Video 8

Reversible pairing of living cells (U937) in the x and y directions by the HANDS platform.

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Yang, S., Tian, Z., Wang, Z. et al. Harmonic acoustics for dynamic and selective particle manipulation. Nat. Mater. 21, 540–546 (2022).

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