Brillouin Microscopy

Overview

Journal Nat Rev Methods Primers

Date 2024 Oct 11

PMID 39391288

Authors

Irina Kabakova

Jitao Zhang

Yuchen Xiang

Silvia Caponi

Alberto Bilenca

Jochen Guck

Giuliano Scarcelli

Affiliations

Soon will be listed here.

Abstract

The field of Brillouin microscopy and imaging was established approximately 20 years ago, thanks to the development of non-scanning high-resolution optical spectrometers. Since then, the field has experienced rapid expansion, incorporating technologies from telecommunications, astrophotonics, multiplexed microscopy, quantum optics and machine learning. Consequently, these advancements have led to much-needed improvements in imaging speed, spectral resolution and sensitivity. The progress in Brillouin microscopy is driven by a strong demand for label-free and contact-free methods to characterize the mechanical properties of biomaterials at the cellular and subcellular scales. Understanding the local biomechanics of cells and tissues has become crucial in predicting cellular fate and tissue pathogenesis. This Primer aims to provide a comprehensive overview of the methods and applications of Brillouin microscopy. It includes key demonstrations of Brillouin microscopy and imaging that can serve as a reference for the existing research community and new adopters of this technology. The article concludes with an outlook, presenting the authors' vision for future developments in this vibrant field. The Primer also highlights specific examples where Brillouin microscopy can have a transformative impact on biology and biomedicine.

Citing Articles

Multimodal Second-Harmonic-Generation, Two-Photon Excitation Fluorescence, and Brillouin Microscopy for Visualising Dermal Mechanical Properties in Ex Vivo Human Skin.

Hase E, Okubo N, Ogura Y, Minamikawa T, Yasui T Exp Dermatol. 2025; 34(3):e70081.

PMID: 40077806 PMC: 11903916. DOI: 10.1111/exd.70081.

Optical, contact-free assessment of brain tissue stiffness and neurodegeneration.

Binner P, Starshynov I, Tejeda G, McFall A, Molloy C, Ciccone G Biomed Opt Express. 2025; 16(2):447-459.

PMID: 39958854 PMC: 11828460. DOI: 10.1364/BOE.545580.

Micromechanical behavior of the apple fruit cuticle investigated by Brillouin light scattering microscopy.

Landes T, Khanal B, Bethge H, Lehrich T, Kilic M, Renz F Commun Biol. 2025; 8(1):174.

PMID: 39905204 PMC: 11794438. DOI: 10.1038/s42003-025-07555-5.

Combining Brillouin Light Scattering Spectroscopy and Machine-Learned Interatomic Potentials to Probe Mechanical Properties of Metal-Organic Frameworks.

Lindner F, Strasser N, Schultze M, Wieser S, Slugovc C, Elsayad K J Phys Chem Lett. 2025; 16(5):1213-1220.

PMID: 39862191 PMC: 11808784. DOI: 10.1021/acs.jpclett.4c03070.

Single-Crystal Elasticity of α-Hydroquinone-An Analogue for Organic Planetary Materials.

Zhang J, Zhou W, Vu T, Hodyss R, Yu X ACS Earth Space Chem. 2025; 9(1):1-7.

PMID: 39839372 PMC: 11744926. DOI: 10.1021/acsearthspacechem.4c00322.

References

Amini R, Bhatnagar A, Schlussler R, Mollmert S, Guck J, Norden C . Amoeboid-like migration ensures correct horizontal cell layer formation in the developing vertebrate retina. Elife. 2022; 11. PMC: 9208757. DOI: 10.7554/eLife.76408. View

Kumar S, Weaver V . Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev. 2009; 28(1-2):113-27. PMC: 2658728. DOI: 10.1007/s10555-008-9173-4. View

Fiore A, Bevilacqua C, Scarcelli G . Direct Three-Dimensional Measurement of Refractive Index via Dual Photon-Phonon Scattering. Phys Rev Lett. 2019; 122(10):103901. PMC: 6530466. DOI: 10.1103/PhysRevLett.122.103901. View

Discher D, Janmey P, Wang Y . Tissue cells feel and respond to the stiffness of their substrate. Science. 2005; 310(5751):1139-43. DOI: 10.1126/science.1116995. View

Patel A, Lee H, Jawerth L, Maharana S, Jahnel M, Hein M . A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation. Cell. 2015; 162(5):1066-77. DOI: 10.1016/j.cell.2015.07.047. View

Zhang J, Scarcelli G . Mapping mechanical properties of biological materials via an add-on Brillouin module to confocal microscopes. Nat Protoc. 2021; 16(2):1251-1275. PMC: 8218248. DOI: 10.1038/s41596-020-00457-2. View

Hu S, Chen J, Fabry B, Numaguchi Y, Gouldstone A, Ingber D . Intracellular stress tomography reveals stress focusing and structural anisotropy in cytoskeleton of living cells. Am J Physiol Cell Physiol. 2003; 285(5):C1082-90. DOI: 10.1152/ajpcell.00159.2003. View

Li Y, Moon S, Chen J, Zhu Z, Chen Z . Ultrahigh-sensitive optical coherence elastography. Light Sci Appl. 2020; 9:58. PMC: 7154028. DOI: 10.1038/s41377-020-0297-9. View

Abuhattum S, Kotzbeck P, Schlussler R, Harger A, Ariza de Schellenberger A, Kim K . Adipose cells and tissues soften with lipid accumulation while in diabetes adipose tissue stiffens. Sci Rep. 2022; 12(1):10325. PMC: 9209483. DOI: 10.1038/s41598-022-13324-9. View

10.

Bradbury P, Cidem A, Mahmodi H, Davies J, Spicer P, Prescott S . Timothy Grass Pollen Induces Spatial Reorganisation of F-Actin and Loss of Junctional Integrity in Respiratory Cells. Inflammation. 2022; 45(3):1209-1223. DOI: 10.1007/s10753-021-01614-9. View

11.

Ballmann C, Thompson J, Traverso A, Meng Z, Scully M, Yakovlev V . Stimulated Brillouin Scattering Microscopic Imaging. Sci Rep. 2015; 5:18139. PMC: 4686920. DOI: 10.1038/srep18139. View

12.

Krafft C, Steiner G, Beleites C, Salzer R . Disease recognition by infrared and Raman spectroscopy. J Biophotonics. 2009; 2(1-2):13-28. DOI: 10.1002/jbio.200810024. View

13.

Elsayad K, Werner S, Gallemi M, Kong J, Sanchez Guajardo E, Zhang L . Mapping the subcellular mechanical properties of live cells in tissues with fluorescence emission-Brillouin imaging. Sci Signal. 2016; 9(435):rs5. DOI: 10.1126/scisignal.aaf6326. View

14.

Griffith L, Swartz M . Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol. 2006; 7(3):211-24. DOI: 10.1038/nrm1858. View

15.

Lee S, Lindsay S, Powell J, Weidlich T, Tao N, Lewen G . A Brillouin scattering study of the hydration of Li- and Na-DNA films. Biopolymers. 1987; 26(10):1637-65. DOI: 10.1002/bip.360261002. View

16.

Baratchi S, Khoshmanesh K, Woodman O, Potocnik S, Peter K, McIntyre P . Molecular Sensors of Blood Flow in Endothelial Cells. Trends Mol Med. 2017; 23(9):850-868. DOI: 10.1016/j.molmed.2017.07.007. View

17.

Zhang J, Raghunathan R, Rippy J, Wu C, Finnell R, Larin K . Tissue biomechanics during cranial neural tube closure measured by Brillouin microscopy and optical coherence tomography. Birth Defects Res. 2018; 111(14):991-998. PMC: 6428642. DOI: 10.1002/bdr2.1389. View

18.

Palombo F, Winlove C, Edginton R, Green E, Stone N, Caponi S . Biomechanics of fibrous proteins of the extracellular matrix studied by Brillouin scattering. J R Soc Interface. 2014; 11(101):20140739. PMC: 4223901. DOI: 10.1098/rsif.2014.0739. View

19.

Matsukawa M, Tsubota R, Kawabe M, Fukui K . Application of a micro-Brillouin scattering technique to characterize bone in the GHz range. Ultrasonics. 2013; 54(5):1155-61. DOI: 10.1016/j.ultras.2013.09.016. View

20.

Zhang J, Nou X, Kim H, Scarcelli G . Brillouin flow cytometry for label-free mechanical phenotyping of the nucleus. Lab Chip. 2017; 17(4):663-670. PMC: 5310767. DOI: 10.1039/c6lc01443g. View