Abstract
Brillouin light scattering (BLS), a technique theoretically described nearly a century back by the French physicist Léon Brillouin in 1922, is a light-scattering method for determining the mechanical properties of materials. This inelastic scattering method is described by the Bragg diffraction of light from a propagating fluctuation in the local dielectric. These fluctuations arise spontaneously from thermally populated sound waves intrinsic to all materials, and thus BLS may be broadly applied to transparent samples of any phase. This review begins with a brief historical overview of the development of BLS, from its theoretical prediction to the current state of the art, and notes specific technological advancements that enabled the development of BLS. Despite the broad utility of BLS, no commercial spectrometer is currently available for purchase, but rather individual components are assembled to suit a specific application. Central to any BLS spectrometer is the interferometer, and its performance characteristics—scanning or non-scanning, multi-passing, and stabilization—are critical considerations for spectrometer design. Consistent with any light-scattering method, the frequency shift is a key observable in BLS, and we summarize the connection of this measurement to evaluate the mechanical properties of materials. With emphasis toward pharmaceutical materials analysis, we introduce the traditional BLS approach for single-crystal elasticity, and this is followed by a discussion of more recent developments in powder BLS. We conclude our review with a perspective on future developments in BLS that may enable BLS as a novel addition to the current catalog of process analytical technologies.
Similar content being viewed by others
References
Siddiqui MR, Al-Othman ZA, Rahman N. Analytical techniques in pharmaceutical analysis: a review. Arab J Chem. 2017;10:S1409–21.
Yu LX, Lionberger RA, Raw AS, D'Costa R, Wu H, Hussain AS. Applications of process analytical technology to crystallization processes. Adv Drug Deliv Rev. 2004;56:349–69.
Rodriquez LO, Alves TP, Cardoso JP, Menezes JC. Improving drug manufacturing with process analytical technology. IDrugs. 2006;9:44–8.
Jamroqiewicz M. Application of the near-infrared spectroscopy in the pharmaceutical technology. J Pharm Biomed Anal. 2012;10:66.
Reich G. Near-infrared spectroscopy and imaging: basic principles and pharmaceutical applications. Adv Drug Deliv Rev. 2005;57:1109–43.
Gowen AA, O'Donnell CP, Cullen PJ, Bell SE. Recent applications of chemical imaging to pharmaceutical process monitoring and quality control. Eur J Pharm Biopharm. 2008;69:10–22.
Gendrin C, Roggo Y, Collet C. Pharmaceutical applications of vibrational chemical imaging and chemometrics: a review. J Pharm Biomed Anal. 2008;48:533–53.
Silva AF, Burggraeve A, Denon Q, Van der Meeran P, Sandler N, Van Den Kerkhof T, et al. Particle sizing measurements in pharmaceutical applications: comparison of in-process methods versus off-line methods. Eur J Pharm Biopharm. 2013;85:1006–18.
Patil SM, Keire DA, Chen K. Comparison of NMR and dynamic light scattering for measuring diffusion coefficients of formulated insulin: implications for particle size distribution measurements in drug products. AAPS J. 2017;19:1760–6.
Chan MY, Dowling QM, Sivananthan SJ, Kramer RM. Particle sizing of nanoparticle adjuvant formulations by dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Methods Mol Biol. 2017;1494:239–52.
De Beer TR, Bodson C, Dejaegher B, Walczak B, Vercruysse P, Burggraeve A, et al. Raman spectroscopy as a process analytical technique technology (PAT) tool for the in-line monitoring and understanding of a powder blending process. J Pharm Biomed Anal. 2008;48:772–9.
De Beer T, Burggraeve A, Fonteyne M, Saerens L, Remon JP, Vervaet C. Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes. Int J Pharm. 2011;417:32–47.
Li YS, Church JS. Raman spectroscopy in the analysis of food and pharmaceutical nanomaterials. J Food Drug Anal. 2014;22:29–48.
Berghaus K, Zhang J, Yun SH, Scarcelli G. High-finesse sub-GHz-resolution spectrometer employing VIPA etalons of different dispersion. Opt Lett. 2015;40:4436–9.
Scarcelli G, Yun SH. Confocal Brillouin microscopy for three-dimensional mechanical imaging. Nat Photonics. 2008;2:39–43.
Scarcelli G, Kim P, Yun SH. In vivo measurement of age-related stiffening in the crystalline lens by Brillouin optical spectroscopy. Biophys J. 2011;101:1539–45.
Coker Z, Troyanova-Wood M, Traverso AJ, Yakupov T, Utegulov ZN, Yakolev VV. Assessing performance of modern Brillouin spectrometers. Opt Express. 2018;26:2400–9.
Meng Z, Bustamante Lopez SC, Meissner KE, Yakovlev VV. Subcellular measurements of mechanical and chemical properties using dual Raman-Brillouin microspectroscopy. J Biophotonics. 2016;9:201–7.
Kuok MH, Lim HS, Ng SC, Liu NN, Wang ZK. Brillouin study of the quantization of acoustic modes in nanospheres. Phys Rev Lett. 2003;90:255502.
Mohapatra H, Kruger TM, Lansakara TI, Tivanski AV, Stevens LL. Core and surface microgel mechanics are differentially sensitive to alternative crosslinking concentrations. Soft Matter. 2017;13:5684–95.
Faurie D, Girodon-Boulandet N, Kaladjian A, Challali F, Abadias G, Djemia P. Setup for high-temperature surface Brillouin light scattering: application to opaque thin films and coatings. Rev Sci Instrum. 2017;88:0293.
Pochylski M, Gapinski J. Simple way to analyze Brillouin spectra from turbid liquids. Opt Lett. 2015;40:1456–9.
Brillouin L. Diffusion de la lumiere et des rayons X par un corps transparent homogene: Influence de l'agitation thermique. Ann Phys (Paris). 1922:88–122.
Mandelstam LI. Light scattering by inhomogeneous media. Zh Russ Fiz-Khim Ova 1926;58:381.
Gross E. Change of wave-length of light due to elastic heat waves at scattering in liquids. Nature. 1930;126:201–2.
Gross E. The splitting of spectral lines at scattering of light by liquids. Nature. 1930;126:400.
Traverso AJ, Thompson JV, Steelman ZA, Meng Z, Scully MO, Yakovlev VV. Dual Raman-Brillouin microscope for chemical and mechanical characterization and imaging. Anal Chem. 2015;87:7519–23.
Meng Z, Thakur T, Chitrakar C, Jaiswal MK, Gaharwar AK, Yakolev VV. Assessment of local heterogeneity in mechanical properties of nanostructured hydrogel networks. ACS Nano. 2017;11:7690–6.
Brewer RG, Rieckhoff KE. The ruby laser as a Brillouin light amplifier. Appl Phys Lett. 1964;5:127–8.
Chiao RY, Stoicheff BP. Brillouin scattering in liquids excited by the helium-neon maser. J Opt Soc Am. 1964;54:1286–7.
Cummins HZ, Gammon RW. Rayleigh and Brillouin scattering in benzene: depolarization factors. Appl Phys Lett. 1965;6:171–3.
Hakim SEA, Comley WJ. Acoustic velocity dispersion in some nonassociated organic liquids. Nature. 1965;208:1082–3.
Venkateswaran CS. Interferometric studies of light scattering in mobile liquids. P Indian Acad Sci A. 1942;15A:322–37.
Grimsditch MH, Ramdas AK. Brillouin scattering in diamond. Phys Rev B. 1975;11:3139–48.
Asenbaum A. Computer-controlled Fabry-Perot interferometer for Brillouin spectroscopy. Appl Opt. 1979;4:363–5.
Roychoudhuri C, Hercher M. Stable multipass Fabry-Perot interferometer: design and analysis. Appl Opt. 1977;16:2514–20.
Dil JG, Van Hijningen NCJA, Van Dorst F. Aarts RM tandem multipass Fabry-Perot interferometer for Brillouin scattering. Appl Opt. 1981;20:1374–81.
Krueger JK, Kimmich R, Sandercock J, Unruh HG. The thermal behavior of n-tetracosane and low molecular weight polyethylene studied by NMR and a refined Brillouin scattering technique. Polym Bull. 1981;5:615–21.
Maret G, Oldenbourg R, Winterling G, Dransfeld K, Rupprecht A. Velocity of high frequency sound waves in oriented DNA fibers and films determined by Brillouin scattering. Colloid Polym Sci. 1979;257:1017–20.
Randall J, Vaughan JM. Brillouin scattering in systems of biological significance. Philos T R Soc A. 1979;293:341–8.
Cusack S, Miller A. Determination of the elastic constants of collagen by Brillouin light scattering. J Mol Biol. 1979;135:39–51.
Zanoni R, Naselli C, Bell J, Stegeman G, Sprague R, Seaton C, et al. Brillouin spectroscopy of Langmuir-Blodgett films. Thin Solid Films. 1985;134:179–86.
Koski KJ, Akhenblit P, McKiernan K, Yarger JL. Non-invasive determination of the complete elastic moduli of spider silks. Nat Mater. 2013;12:262–7.
Gehrsitz S, Sigg H, Siegwart H, Krieger M, Heine C, Morf R, et al. Tandem triple-pass Fabry-Perot interferometer for applications in the near infrared. Appl Opt. 1997;36:5355–61.
Bottari C, Comez L, Paolantoni M, Corezzi S, D'Amico F, Gessini A, et al. Hydration properties and water structure in aqueous solutions of native and modified cyclodextrins by UV Raman and Brillouin scattering. J Raman Spectrosc. 2018;49:1076–85.
Koski KJ, Yarger JL. Brillouin imaging. Appl Phys Lett. 2005;87:061903.
Meng Z, Petrov GI, Yakolev VV. Flow cytometry using Brillouin imaging and sensing via time-resolved optical (BISTRO) measurements. Analyst. 2015;140:7160–4.
Troyanova-Wood M, Gobbell C, Meng Z, Gashev AA, Yakolev VV. Optical assessment of changes in mechanical and chemical properties of adipose tissue in diet-induced obese rats. J Biophotonics. 2017;10:1694–702.
Scarcelli G, Pineda R, Yun SH. Brillouin optical microscopy for corneal biomechanics. Invest Ophthalmol Vis Sci. 2012;53:185–90.
Yun SH, Chernyak D. Brillouin microscopy: assessing ocular tissue biomechanics. Curr Opin Ophthalmol. 2018;29:299–305.
Bottani CE, Fioretto D. Brillouin scattering of phonons in complex materials. Adv Phys X. 2018;3:1467281.
Mueller S, Sandrin L. Liver stiffness: a novel parameter for the diagnosis of liver disease. Hepat Med. 2010;2:49–67.
Wells RG. Tissue mechanics and fibrosis. Biochim Biophys Acta. 1832;2013:884–90.
Fernandes C, Suares D, Yergen MC. Tumor microenvironment targeted nanotherapy. Front Pharmacol. 2018;9:1230.
Palombo C, Kozakova M. Arterial stiffness, atheroschlerosis and cardiovascular risk: pathophysiologic mechanisms and emerging clinical indications. Vasc Pharmacol. 2016;77:1–7.
Meng Z, Basagaoglu B, Yakovlev VV. Atherosclerotic plaque detection by confocal Brillouin and Raman microscopies. in Proc. SPIE 9303, Photonic therapeutics and diagnostics XI, San Francisco, 2015.
Antonacci G, Pedrigi RM, Kondiboyina A, Mehta VV, de Silva R, Paterson C, et al. Quantification of plaque stiffness by Brillouin microscopy in experimental thin cap fibroatheroma. J R Soc Interface. 2015;12:20150843.
Weaver VM. Cell and tissue mechanics: the new cell biology frontier. Mol Biol Cell. 2017;28:1815–8.
Barnes JM, Przybyla L, Weaver VM. Tissue mechanics regulate brain development, homeostasis and disease. J Cell Sci. 2017;130:71–82.
Butler DL, Goldstein SA, Guldberg RE, Guo XE, Kamm R, Laurencin CT, et al. The impact of biomechanics in tissue engineering and regenerative medicine. Tissue Eng Part B Rev. 2009;15:477–84.
Sakamoto M, Kawabe M, Matsukawa M, Koizumi N, Ohtori N. Measurement of wave velocity in bovine bone tissue by micro-Brillouin scattering. Jpn J Appl Phys. 2008;47:4205–8.
Mathieu V, Fukui K, Matsukawa M, Kawabe K, Vayron R, Soffer E, et al. Micro-Brillouin scattering measurements in mature and newly formed bone tissue surrounding an implant. J Biomech Eng. 2011;133:021006.
Akilbekova D, Ogay V, Yakupov T, Sarsenova M, Umbayev B, Tazhin K, et al. Brillouin spectroscopy and radiography for assessment of viscoelastic and regenerative properties of mammalian bone. J Biomed Opt. 2018;23:1–11.
Ingber DE. Cellular mechanotransduction: putting all the pieces together again. FASEB J. 2006;20:811–27.
Wang N. Review of cellular mechanotransduction. J Phys D Appl Phys. 2017;50:233002.
Silver FH, Siperko LM. Mechanosensing and mechanochemical transduction: how is mechanical energy sensed and converted into chemical energy in an extracellular matrix? Crit Rev Biomed Eng. 2003;31:255–331.
Fletcher DA, Mullins RD. Cell mechanics and the cytoskeleton. Nature. 2010;463:485–92.
Xu W, Mezencev R, Kim B, Wang L, McDonald J, Sulchek T. Cell stiffness is a biomarker of the metastatic potential of ovarian cancer. PLoS One. 2012;7:e46609.
Lekka M. Discrimination between normal and cancerous cells using AFM. BioNanoSci. 2016;6:65–80.
Islam M, Mezencev R, McFarland B, Brink H, Campbell B, Tasadduq B, et al. Microfluidic cell sorting by stiffness to examine heterogenic responses of cancer cells to chemotherapy. Cell Death Dis. 2018;9:239.
Zoellner H, Paknejad N, Manova K, Moore M. A novel cell-stiffness-fingerprinting analysis by scanning atomic force microscopy: comparison of fibroblasts and diverse cancer cell lines. Histochem Cell Biol. 2015;144:533–42.
Kilpatrick JI, Revenko I, Rodriquez BJ. Nanomechanics of cells and biomaterials studied by atomic force microscopy. Adv Healthc Mater. 2015;4:2456–74.
Scarcelli G, Polacheck WJ, Nia HT, Patel K, Grodzinsky AJ, Kamm RD, et al. Noncontact three-dimensional mapping of intracellular hydromechanical properties by Brillouin microscopy. Nat Methods. 2015;12:1132–4.
Meng Z, Traverso AJ, Ballmann CW, Troyanova-Wood MA, Yakovlev VV. Seeing cells in a new light: a renaissance of Brillouin spectroscopy. Adv Opt Photon. 2016;8:300–26.
Antonacci G, Braakman S. Biomechanics of subcellular structures by non-invasive Brillouin microscopy. Sci Rep. 2016;6:37217.
Mattana S, Mattarelli M, Urbanelli L, Sagini K, Emiliani C, Serra MD, et al. Non-contact mechanical and chemical analysis of single living cells by microspectroscopic techniques. Light Sci Appl. 2018;7:17139.
Basoli F, Giannitelli SM, Gori M, Mozetic P, Bonfanti A, Trombetta M, et al. Biomechanical characterization at the cell scale: present and prospects. Front Physiol. 2018;15:1449.
Guo P, Liu D, Subramanyam K, Wang B, Yang J, Huang J, et al. Nanoparticle elasticity directs tumor uptake. Nat Commun. 2018;9:130.
Anselmo AC, Zhang M, Kumar S, Vogus DR, Menegatti S, Helgeson ME, et al. Elasticity of nanoparticles influences their blood circulation, phagocytosis, endocytosis, and targeting. ACS Nano. 2015;9:3169–77.
Anselmo AC, Mitragotri S. Impact of particle elasticity on particle-based drug delivery systems. Adv Drug Deliv Rev. 2017;108:51–67.
Cheng W, Wang JJ, Jonas U, Steffen W, Fytas G, Penciu R, et al. The spectrum of vibrational modes in soft opals. J Chem Phys. 2005;123:121104.
Still T, Mattarelli M, Kiefer D, Fytas G, Montagna M. Eigenvibrations of submicrometer colloidal spheres. J Phys Chem Lett. 2010;1:2440–4.
Still T, Cheng W, Retsch M, Jonas U, Fytas G. Colloidal systems: a promising material class for tailoring sound propagation at high frequencies. J Phys:Condens Matter. 2008;20:404203.
Mattarelli M, Montagna M, Still T, Schneider D, Fytas G. Vibration spectroscopy of weakly interacting mesoscopic colloids. Soft Matter. 2012;8:4235–43.
Love AEH. A treatise on the mathematical theory of elasticity. New York: Dover Publications; 1944.
Cummins HZ, Schoen PE. in Laser Handbook. Amsterdam: North Holland Publishing Co.; 1971. p. E1.
Dil JG. Brillouin scattering in condensed matter. Rep Prog Phys. 1982;45:285–334.
Chu B. Laser scattering. J Chem Ed. 1968;45:224–30.
Kruger JK, Marx A, Peetz L, Roberts R, Unruh HG. Simultaneous determination of elastic and optical properties of polymers by high performance Brillouin spectroscopy using different scattering geometries. Colloid Polym Sci. 1986;264:403–14.
Xu J, Ren X, Gong W, Dai R, Liu D. Measurement of the bulk viscosity of liquid by Brillouin scattering. Appl Opt. 2003;42:6704–9.
Ballmann CW, Meng Z, Traverso AJ, Scully MO, Yakovlev VV. Impulsive Brillouin microscopy. Optica. 2017;4:124–8.
Bencivenga F, Battistoni A, Fioretto D, Gessini A, Sandercock JR, Masciovecchio C. A high resolution ultraviolet Brillouin scattering set-up. Rev Sci Instrum. 2012;83:103102.
Antonacci G, de Turris V, Rosa A, Ruocco G. Background-deflection Brillouin microscopy reveals altered biomechanics of intracellular stress granules by ALS protein FUS. Commun Bio. 2018;1:139.
Fiore A, Zhang J, Shao P, Yun SH, Scarcelli G. High-extinction virtually imaged phased array-based Brillouin spectroscopy of turbid biological media. Appl Phys Lett. 2016;108:203701.
Meng Z, Yakovlev VV. Precise determination of Brillouin scattering spectrum using a virtually imaged phase array (VIPA) spectrometer and charge-coupled device (CCD) camera. Appl Spectrosc. 2016;70:1356–63.
Abell BC, Shao S, Pyrak-Nolte LJ. Measurement of elastic constants in anisotropic media. Geophysics. 2014;79:D349–62.
Newnham R. Properties of materials. New York: Oxford University Press; 2005.
Nye JF. Physical properties of crystals. New York: Oxford University Press; 1957.
Karki S, Friscic T, Fabian L, Laity PR, Day GR, Jones W. Improving mechanical properties of crystalline solids by cocrystal formation: new compressible forms of paracetamol. Adv Mater. 2009;21:3905–9.
Beyer T, Day GM, Price SL. The prediction, morphology, and mechanical properties of polymorphs of paracetamol. J Am Chem Soc. 2001;123:5086–94.
Ortiz AU, Boutin A, Fuchs AH, Coudert FX. Anisotropic elastic properties of flexible metal-organic frameworks: how soft are soft porous crystals? Phys Rev Lett. 2012;109:195502.
Turley J, Sines G. The anisotropy of Young’s modulus, shear modulus and Poisson’s ratio in cubic materials. J Phys D:Appl Phys. 1971;4:264–71.
Mohapatra H, Eckhardt CJ. Elastic constants and related mechanical properties of the monoclinic polymorph of the carbamazepine molecular crystal. J Phys Chem B. 2008;112:2293–8.
Eros S, Reitz JR. Elastic constants by the ultrasonic pulse echo method. J Appl Phys. 1958;29:683–6.
Zeng Z, Tan JC. AFM nanoindentation to quantify mechanical properties of nano- and micron-sized crystals of a metal-organic framework. ACS Appl Mater Interfaces. 2017;9:39839–54.
Stevens LL, Hooks DE, Migliori A. A comparative evaluation of elasticity in pentaerythritol tetranitrate using Brillouin scattering and resonant ultrasound spectroscopy. J Appl Phys. 2010;108:053512.
Hernandez J, Li G, Cummins HZ, Callender RH. Low-frequency light-scattering spectroscopy of powders. J Opt Soc Am B. 1996;13:1130–4.
Singaraju AB, Nguyen K, Jain A, Haware RV, Stevens LL. Aggregate elasticity, crystal structure and tableting performance for p-aminobenzoic acid and a series of its benzoate esters. Mol Pharm. 2016;13:3794–806.
Singaraju AB, Iyer M, Haware RV, Stevens LL. Caffeine co-crystal mechanics evaluated with a combined structural and spectroscopic approach. Cryst Growth Des. 2016;16:4383–91.
Almarsson O, Zaworotko MJ. Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improve medicines? Chem Commun. 2004;17:1889–96.
Steed JW. The role of co-crystals in pharmaceutical design. Trends Pharmacol Sci. 2013;34:185–93.
Stephen Chan HC, Kendrick J, Neumann MA, Leusen FJJ. Towards ab initio screening of co-crystal formation through lattice energy calculations and crystal structure prediction of multi-component crystals. CrystEngComm. 2013;15:3799–807.
Desiraju GR. Crystal engineering: from molecule to crystal. J Am Chem Soc. 2013;135:9952–67.
Singaraju AB, Nguyen K, Swenson DC, Iyer M, Haware RV, Stevens LL. Reorganized, weak C-H…O interactions directly modify the mechanical properties and compaction performance of a series of nitrobenzoic acids. CrystEngComm. 2017;19:2526–35.
Singaraju AB, Nguyen K, Gawedski P, Herald F, Meyer G, Wentworth D, et al. Combining crystal structure and interaction topology for interpreting functional molecular solids: a study of theophylline cocrystals. Cryst Growth Des. 2017;17:6741–51.
Author information
Authors and Affiliations
Corresponding author
Additional information
Guest Editors: William C. Stagner and Rahul V. Haware
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Singaraju, A.B., Bahl, D. & Stevens, L.L. Brillouin Light Scattering: Development of a Near Century-Old Technique for Characterizing the Mechanical Properties of Materials. AAPS PharmSciTech 20, 109 (2019). https://doi.org/10.1208/s12249-019-1311-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1208/s12249-019-1311-5