Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Single-particle photoacoustic vibrational spectroscopy using optical microresonators

Nature Photonics volume 17, pages 951–956 (2023)Cite this article

Subjects

Abstract

Vibrational spectroscopy is a ubiquitous technology that derives the species, constituents and morphology of an object from its natural vibrations. However, natural vibrations of mesoscopic particles—including most biological cells—have remained hidden from existing technologies. These particles are expected to vibrate faintly at megahertz to gigahertz rates, requiring a sensitivity and resolution that are impractical for current optical and piezoelectric spectroscopies. Here we demonstrate the real-time measurement of natural vibrations of single mesoscopic particles using an optical microresonator, extending the reach of vibrational spectroscopy to a different spectral window. Conceptually, a spectrum of vibrational modes of the particles is stimulated photoacoustically by the absorption of laser pulses and acoustically coupled to a high-quality-factor optical resonance for ultrasensitive readout. Experimentally, this scheme is verified by measuring mesoscopic particles with different constituents, sizes and internal structures, showing an unprecedented signal-to-noise ratio of 50 dB and detection bandwidth of over 1 GHz. This technology is further applied for the biomechanical fingerprinting of the species and living states of microorganisms at the single-cell level. This work opens up new avenues to study single-particle mechanical properties in vibrational degrees of freedom and may find applications in photoacoustic sensing and imaging, cavity optomechanics and biomechanics.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Microresonator-based vibrational spectroscopy.
Fig. 2: Temporal and spectral measurement of natural vibrations of a single particle.
Fig. 3: Mechanical fingerprinting of mesoscopic particles with different sizes and internal structures.
Fig. 4: Biomechanical fingerprinting of microbial cells.

Data availability

The data that supports the plots within this paper are available on Figshare (https://doi.org/10.6084/m9.figshare.22718299). All other data used in this study are available from the corresponding authors upon reasonable request.

Code availability

The codes are available from the corresponding author upon reasonable request.

References

  1. Pelling, AE, Sehati, S, Gralla, EB, Valentine, JS & Gimzewski, JK Local nanomechanical motion of the cell wall of Saccharomyces cerevisiae. Science 305, 1147–1150 (2004).

    ADS  Google Scholar 

  2. Chaplin, W & Miglio, A Asteroseismology of solar-type and red-giant stars. Annu. Rev. Astron. Astrophys. 51, 353–392 (2013).

    ADS  Google Scholar 

  3. Vittoz, E. Low-Power Crystal and MEMS Oscillators: the Experience of Watch Developments (Springer, 2010).

  4. Diem, M. Modern Vibrational Spectroscopy and Micro-Spectroscopy (Wiley, 2015).

  5. Coutaz, J.-L., Garet, F. & Wallace, V. Principles of Terahertz Time-Domain Spectroscopy (CRC Press, 2018).

  6. LeCraw, R, Spencer, E & Gordon, E Extremely low loss acoustic resonance in single-crystal garnet spheres. Phys. Rev. Lett. 6, 620–622 (1961).

    ADS  Google Scholar 

  7. Keshtgar, H, Streib, S, Kamra, A, Blanter, YM & Bauer, GE Magnetomechanical coupling and ferromagnetic resonance in magnetic nanoparticles. Phys. Rev. B 95, 134447 (2017).

    ADS  Google Scholar 

  8. Zhang, X, Zou, C-L, Jiang, L & Tang, HX Cavity magnomechanics. Sci. Adv. 2, e1501286 (2016).

    ADS  Google Scholar 

  9. Tayebi, M et al. Massively multiplexed submicron particle patterning in acoustically driven oscillating nanocavities. Small 16, 2000462 (2020).

    Google Scholar 

  10. Ackerman, E Resonances of biological cells at audible frequencies. Bull. Math. Biol. 13, 93–106 (1951).

    Google Scholar 

  11. Zinin, P, Allen, JIII & Levin, V Mechanical resonances of bacteria cells. Phys. Rev. E 72, 061907 (2005).

    ADS  Google Scholar 

  12. Dykeman, EC & Sankey, OF Low frequency mechanical modes of viral capsids: an atomistic approach. Phys. Rev. Lett. 100, 028101 (2008).

    ADS  Google Scholar 

  13. Zinin, PV & Allen, JSIII Deformation of biological cells in the acoustic field of an oscillating bubble. Phys. Rev. E 79, 021910 (2009).

    ADS  Google Scholar 

  14. Tsen, S-WD, Wu, TC, Kiang, JG & Tsen, K-T Prospects for a novel ultrashort pulsed laser technology for pathogen inactivation. J. Biomed. Sci. 19, 62 (2012).

    Google Scholar 

  15. Pelton, M et al. Damping of acoustic vibrations in gold nanoparticles. Nat. Nanotechnol. 4, 492–495 (2009).

    ADS  Google Scholar 

  16. Crut, A, Maioli, P, Del Fatti, N & Vallée, F Optical absorption and scattering spectroscopies of single nano-objects. Chem. Soc. Rev. 43, 3921–3956 (2014).

    Google Scholar 

  17. Zhou, J, Chizhik, AI, Chu, S & Jin, D Single-particle spectroscopy for functional nanomaterials. Nature 579, 41–50 (2020).

    ADS  Google Scholar 

  18. Guck, J et al. The optical stretcher: a novel laser tool to micromanipulate cells. Biophys. J. 81, 767–784 (2001).

    ADS  Google Scholar 

  19. Rojas, ER et al. The outer membrane is an essential load-bearing element in gram-negative bacteria. Nature 559, 617–621 (2018).

    ADS  Google Scholar 

  20. Krieg, M et al. Atomic force microscopy-based mechanobiology. Nat. Rev. Phys. 1, 41–57 (2019).

    Google Scholar 

  21. Horace Lamb, MA On the vibrations of an elastic sphere. Proc. London Math. Soc. 13, 189–212 (1882).

    MathSciNet  MATH  Google Scholar 

  22. Galstyan, V, Pak, OS & Stone, HA A note on the breathing mode of an elastic sphere in newtonian and complex fluids. Phys. Fluids 27, 032001 (2015).

    ADS  Google Scholar 

  23. Scarcelli, G & Yun, SH Confocal Brillouin microscopy for three-dimensional mechanical imaging. Nat. Photon. 2, 39–43 (2008).

    ADS  Google Scholar 

  24. Wheaton, S, Gelfand, RM & Gordon, R Probing the Raman-active acoustic vibrations of nanoparticles with extraordinary spectral resolution. Nat. Photon. 9, 68–72 (2015).

    ADS  Google Scholar 

  25. Langer, J et al. Present and future of surface-enhanced Raman scattering. ACS Nano 14, 28–117 (2019).

    Google Scholar 

  26. Qiu, L et al. A high-precision multi-dimensional microspectroscopic technique for morphological and properties analysis of cancer cell. Light Sci. Appl. 12, 129 (2023).

    ADS  Google Scholar 

  27. Leisure, RG & Willis, F Resonant ultrasound spectroscopy. J. Phys. Condens. Matter 9, 6001 (1997).

    ADS  Google Scholar 

  28. Wissmeyer, G, Pleitez, MA, Rosenthal, A & Ntziachristos, V Looking at sound: optoacoustics with all-optical ultrasound detection. Light Sci. Appl. 7, 53 (2018).

    ADS  Google Scholar 

  29. Gil-Santos, E et al. Optomechanical detection of vibration modes of a single bacterium. Nat. Nanotechnol. 15, 469–474 (2020).

    ADS  Google Scholar 

  30. Chen, W, Kaya Özdemir, Ş, Zhao, G, Wiersig, J & Yang, L Exceptional points enhance sensing in an optical microcavity. Nature 548, 192–196 (2017).

    ADS  Google Scholar 

  31. Lai, Y-H, Lu, Y-K, Suh, M-G, Yuan, Z & Vahala, K Observation of the exceptional-point-enhanced Sagnac effect. Nature 576, 65–69 (2019).

    ADS  Google Scholar 

  32. Yu, D et al. Whispering-gallery-mode sensors for biological and physical sensing. Nat. Rev. Methods Primers 1, 83 (2021).

    Google Scholar 

  33. Westerveld, WJ et al. Sensitive, small, broadband and scalable optomechanical ultrasound sensor in silicon photonics. Nat. Photon. 15, 341–345 (2021).

    ADS  Google Scholar 

  34. Meng, J-W et al. Dissipative acousto-optic interactions in optical microcavities. Phys. Rev. Lett. 129, 073901 (2022).

    ADS  Google Scholar 

  35. Toropov, N et al. Review of biosensing with whispering-gallery mode lasers. Light Sci. Appl. 10, 42 (2021).

    ADS  Google Scholar 

  36. Wang, LV & Yao, J A practical guide to photoacoustic tomography in the life sciences. Nat. Methods 13, 627–638 (2016).

    Google Scholar 

  37. Strohm, EM, Moore, MJ & Kolios, MC Single cell photoacoustic microscopy: a review. IEEE J. Sel. Top. Quantum Electron. 22, 137–151 (2015).

    ADS  Google Scholar 

  38. Tan, Z et al. Multimodal subcellular imaging with microcavity photoacoustic transducer. Opt. Express 19, 2426–2431 (2011).

    ADS  Google Scholar 

  39. Strohm, EM, Berndl, ES & Kolios, MC Probing red blood cell morphology using high-frequency photoacoustics. Biophys. J. 105, 59–67 (2013).

    ADS  Google Scholar 

  40. Strohm, EM & Kolios, MC Classification of blood cells and tumor cells using label-free ultrasound and photoacoustics. Cytometry A 87, 741–749 (2015).

    Google Scholar 

  41. Ma, R et al. Radiation-pressure-driven vibrational modes in ultrahigh-Q silica microspheres. Opt. Lett. 32, 2200–2202 (2007).

    ADS  Google Scholar 

  42. Shen, Z et al. Coherent coupling between phonons, magnons and photons. Phys. Rev. Lett. 129, 243601 (2022).

    ADS  Google Scholar 

  43. Li, C & Wang, LV Photoacoustic tomography and sensing in biomedicine. Phys. Med. Biol. 54, R59–R97 (2009).

    ADS  Google Scholar 

  44. Woo, I-S, Rhee, I-K & Park, H-D Differential damage in bacterial cells by microwave radiation on the basis of cell wall structure. Appl. Environ. Microbiol. 66, 2243–2247 (2000).

    ADS  Google Scholar 

  45. Pillet, F et al. Uncovering by atomic force microscopy of an original circular structure at the yeast cell surface in response to heat shock. BMC Biol. 12, 6 (2014).

    Google Scholar 

  46. Yu, W, Jiang, WC, Lin, Q & Lu, T Cavity optomechanical spring sensing of single molecules. Nat. Commun. 7, 12311 (2016).

    ADS  Google Scholar 

  47. Sansa, M et al. Optomechanical mass spectrometry. Nat. Commun. 11, 3781 (2020).

    ADS  Google Scholar 

  48. Sbarra, S et al. Multimode optomechanical weighting of a single nanoparticle. Nano Lett. 22, 710–715 (2022).

    ADS  Google Scholar 

  49. Han, K, Kim, J & Bahl, G High-throughput sensing of freely flowing particles with optomechanofluidics. Optica 3, 585–591 (2016).

    ADS  Google Scholar 

  50. Fan, X & Yun, S-H The potential of optofluidic biolasers. Nat. Methods 11, 141–147 (2014).

    Google Scholar 

  51. Mittelstein, DR et al. Selective ablation of cancer cells with low intensity pulsed ultrasound. Appl. Phys. Lett. 116, 013701 (2020).

    ADS  Google Scholar 

  52. Wierzbicki, T, Li, W, Liu, Y & Zhu, J Effect of receptors on the resonant and transient harmonic vibrations of coronavirus. J. Mech. Phys. Solids 150, 104369 (2021).

    MathSciNet  Google Scholar 

  53. Sadraeian, M, Zhang, L, Aavani, F, Biazar, E & Jin, D Viral inactivation by light. eLight 2, 18 (2022).

    Google Scholar 

Download references

Acknowledgements

We thank X.-C. Yu, G. Li, C. Li and J. Huang for helpful discussions. S.-J.T., J.S. and Y.F.X. thank J. Zhao and Y. Ji at Peking University for their help in bacteria experiments. This project is supported by the National Natural Science Foundation of China (grants nos. 11825402, 12293051, 62105006, 12041602, 62175002, 92150108 and 92150301), and Beijing Natural Science Foundation (no. Z210004). S.-J.T. was also supported by the China Postdoctoral Science Foundation (grant nos. 2021T140023 and 2020M680187). Parts of the characterization and simulation are supported by the Peking Nanofab, Core Facilities of Life Sciences and High-Performance Computing Platform of Peking University.

Author information

Authors and Affiliations

  1. Frontiers Science Center for Nano-optoelectronics and State Key Laboratory for Mesoscopic Physics, School of Physics, Peking University, Beijing, China

    Shui-Jing Tang, Mingjie Zhang, Jia-Wei Meng, Xiao Xiong, Qihuang Gong, Qi-Fan Yang & Yun-Feng Xiao

  2. National Biomedical Imaging Center, Peking University, Beijing, China

    Jialve Sun & Yun-Feng Xiao

  3. Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan, China

    Qihuang Gong, Qi-Fan Yang & Yun-Feng Xiao

  4. Institute for Biomedical Materials and Devices (IBMD), Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia

    Dayong Jin

Authors
  1. Shui-Jing Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mingjie Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jialve Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jia-Wei Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qihuang Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dayong Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qi-Fan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yun-Feng Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.-J.T. designed and performed the experiments with the help of J.S. and J.-W.M. M.Z. provided theoretical analyses under the guidance of S.-J.T. J.S. developed methods to transfer single particles and microorganisms. S.-J.T., Q.-F.Y., M.Z., X.X. and Y.-F.X. wrote the manuscript with contributions from all authors. Y.-F.X. conceived the idea and supervised the project.

Corresponding author

Correspondence to Yun-Feng Xiao.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Photonics thanks the anonymous reviewers for their contribution to the peer review of this work.

Additional information

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

Extended data

Extended Data Fig. 1 Photoacoustic excitation of particle’s vibrations.

a, Light absorption of a short laser pulse excites mechanical resonances of the particle. Top panel: the laser pulse; Bottom panel: the particle’s surface displacement (Curve: theoretical model; Circles: three-dimensional finite-element method). b, Simulated temperature map when the particle is irradiated by a short laser pulse. c, Excited oscillation shapes of breathing, even and odd vibrational modes when the laser pulse is irradiated from the top as shown in b. d, Vibrational spectrum of the spherical particle at the contact site (blue dot in b) is obtained from the theoretical displacement evolution. The frequency is normalized to the natural frequency of the (1,0) mode. The parameters of the spherical particle used in both theoretical and simulation model: 500 nm in radius, E = 500 MPa, ρ = 1.0 g cm−3, Poisson’s ratio σ = 0.35, refractive index n = 1.75 + 0.005i, heat capacity Cp = 1300 J/(kg ⋅ K), and thermal expansion coefficient αth = 2.4 × 10−4. The heat conductivity coefficient κh = 0.08 W/(m ⋅ K) is used in the simulation.

Extended Data Fig. 2 Identifications of vibrational modes.

a-b, Vibrational spectra obtained when a 1.1-μm-radius polystyrene sphere is deposited on the microresonator’s surface and irradiated by laser pulses with the pulse duration of 200 ps (a), and 1.8 ns (b), respectively. Vibrational modes of the particle are indicated with the red shadows. c, Vibrational spectra obtained with the intracavity radiation pressure to identify the vibrational modes of the silica microsphere (dashed lines labelled).

Extended Data Fig. 3 Temporal and spectral characterization of natural vibrations of single microbial cells.

Laser transmission (a) and corresponding vibrational spectra (b) of a single Aspergillus niger spore (i), Aspergillus Sydowii (ii) and cyanobacterium (iii). The navy and red curves are experimental data and fittings, respectively. Vibrations of the microresonator are also indicated. The mode indices of these vibrational modes are identified by matching the spectral features to numerical calculations. The (1,0) breathing mode could not be supported in microbial cells because of the incompressible property of their cytoplasm (Supplementary Note II for details). The quality factors of the vibrational modes of microbial cells are within 5 ~ 30. In these measurements, the microbial cells are placed on the microspherical optical cavity about 10 ~ 20 μm away from its equator. Insets: SEM and TEM images of microbial cells. Scale bars: 1 μm.

Supplementary information

Supplementary Information

Supplementary sections 1 and 2 and Figs. 1–7.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tang, SJ., Zhang, M., Sun, J. et al. Single-particle photoacoustic vibrational spectroscopy using optical microresonators. Nat. Photon. 17, 951–956 (2023). https://doi.org/10.1038/s41566-023-01264-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41566-023-01264-3

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing