{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T01:26:57Z","timestamp":1780968417533,"version":"3.54.1"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["AP14972763"],"award-info":[{"award-number":["AP14972763"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>Noninvasive in situ monitoring of viscoelastic characteristics of corneal tissue at elevated temperatures is pivotal for mechanical property-informed refractive surgery techniques, including thermokeratoplasty and photorefractive keratectomy, requiring precise thermal modifications of the corneal structure during these surgical procedures. This study harnesses Brillouin light scattering spectroscopy as a biosensing platform to noninvasively probe the viscoelastic properties of ovine corneas across a temperature range of 25\u201364 \u00b0C. By submerging the tissue samples in silicone oil, consistent hydration and immiscibility are maintained, allowing for their accurate sensing of temperature-dependent mechanical behaviors. We identify significant phase transitions in the corneal tissue, particularly beyond 40 \u00b0C, likely due to collagen unfolding, marking the beginning of thermal destabilization. A subsequent transition, observed beyond 60 \u00b0C, correlates with collagen denaturation. These phase transformations highlight the cornea\u2019s sensitivity to both physiologically reversible and irreversible viscoelastic changes induced by mild to high temperatures. Our findings underscore the potential of the Brillouin biosensing technique for real-time diagnostics of corneal biomechanics during refractive surgeries to attain optimized therapeutic outcomes.<\/jats:p>","DOI":"10.3390\/bios14080371","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T15:25:23Z","timestamp":1722353123000},"page":"371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Brillouin Biosensing of Viscoelasticity across Phase Transitions in Ovine Cornea"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0683-0374","authenticated-orcid":false,"given":"Chingis","family":"Kharmyssov","sequence":"first","affiliation":[{"name":"Department of Science, Astana IT University, Astana 020000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7574-9070","authenticated-orcid":false,"given":"Zhandos","family":"Utegulov","sequence":"additional","affiliation":[{"name":"Department of Physics, School of Sciences and Humanities, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/S0886-3350(88)80063-4","article-title":"Photorefractive Keratectomy: A Technique for Laser Refractive Surgery","volume":"14","author":"Munnerlyn","year":"1988","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1038\/s41433-022-02174-4","article-title":"Transepithelial Photorefractive Keratectomy: A Prospective Randomized Comparative Study between the Two-Step and the Single-Step Techniques","volume":"37","author":"Shehata","year":"2023","journal-title":"Eye"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1002\/lsm.23495","article-title":"Keratometry and Ultrastructural Changes after Microwave Thermokeratoplasty in Rabbit Eyes","volume":"54","author":"Sun","year":"2021","journal-title":"Lasers Surg. Med."},{"key":"ref_4","first-page":"149","article-title":"Corneal Regeneration after Photorefractive Keratectomy: A Review","volume":"8","author":"Hanneken","year":"2014","journal-title":"J. Optom."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/S0886-3350(98)80011-4","article-title":"Diode Laser Thermokeratoplasty: Application Strategy and Dosimetry","volume":"24","author":"Brinkmann","year":"1998","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0002-9394(02)01942-6","article-title":"Mathematical Model of Corneal Surface Smoothing after Laser Refractive Surgery","volume":"135","author":"Huang","year":"2003","journal-title":"Am. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5653","DOI":"10.1088\/0031-9155\/55\/19\/003","article-title":"Numerical Model of Heat Transfer in the Human Eye with Consideration of Fluid Dynamics of the Aqueous Humour","volume":"55","author":"Karampatzakis","year":"2010","journal-title":"Phys. Med. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1007\/s11517-019-01983-2","article-title":"Optic Nerve Head Damage Relation to Intracranial Pressure and Corneal Properties of Eye in Glaucoma Risk Assessment","volume":"57","author":"Kharmyssov","year":"2019","journal-title":"Med Biol. Eng. Comput."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nimni, M.E., and Harkness, R.D. (2018). Molecular Structure and Functions of Collagen. Collagen: Volume I: Biochemistry, CRC Press.","DOI":"10.1201\/9781351070799"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/j.1751-1097.1991.tb09897.x","article-title":"Pathologic analysis of photothermal and photomechanical effects of laser\u2013tissue interactions","volume":"53","author":"Thomsen","year":"1991","journal-title":"Photochem. Photobiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1159\/000076150","article-title":"Thermomechanical Behavior of Collagen-Cross-Linked Porcine Cornea","volume":"218","author":"Spoerl","year":"2004","journal-title":"Ophthalmologica"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1042\/bj3220535","article-title":"Chemistry of Collagen Cross-Linking: Biochemical Changes in Collagen during the Partial Mineralization of Turkey Leg Tendon","volume":"322","author":"Knott","year":"1997","journal-title":"Biochem. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1002\/app.22711","article-title":"Thermal Properties Measurements of Renatured Gelatin Using Conventional and Temperature Modulated Differential Scanning Calorimetry","volume":"99","author":"Dai","year":"2005","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.bpj.2011.04.033","article-title":"Thermal Denaturation Studies of Collagen by Microthermal Analysis and Atomic Force Microscopy","volume":"101","author":"Bozec","year":"2011","journal-title":"Biophys. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kurbanova, B., Ashikbayeva, Z., Amantayeva, A., Sametova, A., Blanc, W., Gaipov, A., Tosi, D., and Utegulov, Z. (2022). Thermo-Visco-Elastometry of RF-Wave-Heated and Ablated Flesh Tissues Containing Au Nanoparticles. Biosensors, 13.","DOI":"10.3390\/bios13010008"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Akilbekova, D., Yakupov, T., Ogay, V., Umbayev, B., Yakovlev, V.V., and Utegulov, Z.N. (2018). Brillouin Light Scattering Spectroscopy for Tissue Engineering Application. Optical Elastography and Tissue Biomechanics V, SPIE.","DOI":"10.1117\/12.2289923"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1364\/OE.26.002400","article-title":"Assessing Performance of Modern Brillouin Spectrometers","volume":"26","author":"Coker","year":"2018","journal-title":"Opt. Express"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kharmyssov, C., Sekerbayev, K., Nurekeyev, Z., Gaipov, A., and Utegulov, Z.N. (2023). Mechano-Chemistry across Phase Transitions in Heated Albumin Protein Solutions. Polymers, 15.","DOI":"10.3390\/polym15092039"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1167\/iovs.11-8281","article-title":"Brillouin Optical Microscopy for Corneal Biomechanics","volume":"53","author":"Scarcelli","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1167\/iovs.12-11387","article-title":"Brillouin Microscopy of Collagen Crosslinking: Noncontact Depth-Dependent Analysis of Corneal Elastic Modulus","volume":"54","author":"Scarcelli","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4490","DOI":"10.1167\/iovs.14-14450","article-title":"Biomechanical Characterization of Keratoconus Corneas Ex Vivo with Brillouin Microscopy","volume":"55","author":"Scarcelli","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"721","DOI":"10.3928\/1081597X-20191004-01","article-title":"Depth-Dependent Reduction of Biomechanical Efficacy of Contact Lens\u2013Assisted Corneal Cross-Linking Analyzed by Brillouin Microscopy","volume":"35","author":"Zhang","year":"2019","journal-title":"J. Refract. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1001\/jamaophthalmol.2014.5641","article-title":"In Vivo Biomechanical Mapping of Normal and Keratoconus CorneasIn Vivo Biomechanical Mapping of CorneasLetters","volume":"133","author":"Scarcelli","year":"2015","journal-title":"JAMA Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Akilbekova, D., Ogay, V., Yakupov, T., Sarsenova, M., Umbayev, B., Nurakhmetov, A., Tazhin, K., Yakovlev, V.V., and Utegulov, Z.N. (2018). Brillouin Spectroscopy and Radiography for Assessment of Viscoelastic and Regenerative Properties of Mammalian Bones. J. Biomed. Opt., 23.","DOI":"10.1117\/1.JBO.23.9.097004"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1007\/s00417-018-4069-7","article-title":"The Influence of Hydration on Different Mechanical Moduli of the Cornea","volume":"256","author":"Seiler","year":"2018","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1167\/iovs.18-24228","article-title":"Effects of Corneal Hydration on Brillouin Microscopy in Vivo","volume":"59","author":"Shao","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/jctb.2331","article-title":"Silicone Oil: An Effective Absorbent for the Removal of Hydrophobic Volatile Organic Compounds","volume":"85","author":"Darracq","year":"2010","journal-title":"J. Chem. Technol. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.exer.2013.11.017","article-title":"Effects of Bathing Solution on Tensile Properties of the Cornea","volume":"120","author":"Rahimi","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"38056","DOI":"10.1039\/C5RA03817K","article-title":"Acoustic and Elastic Properties of Silicone Oil under High Pressure","volume":"5","author":"Wang","year":"2015","journal-title":"RSC Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1073\/pnas.032307099","article-title":"Type I Collagen Is Thermally Unstable at Body Temperature","volume":"99","author":"Leikina","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/00003226-200005000-00020","article-title":"Thermal and Biomechanical Parameters of Porcine Cornea","volume":"19","author":"Kampmeier","year":"2000","journal-title":"Cornea"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Iannucci, L.E., Riak, M.B., Meitz, E., Bersi, M.R., Gruev, V., and Lake, S.P. (2023). Effect of Matrix Properties on Transmission and Reflectance Mode Division-of-Focal-Plane Stokes Polarimetry. J. Biomed. Opt., 28.","DOI":"10.1117\/1.JBO.28.10.102902"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10901","DOI":"10.1021\/jacs.3c00713","article-title":"The Chemistry and Biology of Collagen Hybridization","volume":"145","author":"Li","year":"2023","journal-title":"J. Am. Chem. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1080\/00222348.2013.852059","article-title":"Viscosity of Collagen Solutions: Influence of Concentration, Temperature, Adsorption, and Role of Intermolecular Interactions","volume":"53","author":"Li","year":"2014","journal-title":"J. Macromol. Sci. Part B Phys."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Brinkmann, R., Koop, N., Ksmpmeier, J., Bruhns, A., Asiyo-Vogel, M., Engelhardt, R., and Birngruber, R. (1997). Corneal Collagen Denaturation in Laser Thermokeratoplasty (LTK). Investig. Ophthalmol. Vis. Sci., 38.","DOI":"10.1117\/12.239611"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7161","DOI":"10.1021\/bi00444a005","article-title":"Monomer and Oligomer of Type I Collagen: Molecular Properties and Fibril Assembly","volume":"28","author":"Na","year":"1989","journal-title":"Biochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4881","DOI":"10.1016\/S0142-9612(03)00369-7","article-title":"Thermal Assembly of a Biomimetic Mineral\/Collagen Composite","volume":"24","author":"Pederson","year":"2003","journal-title":"Biomaterials"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1080\/00222348.2010.518540","article-title":"Viscometric Study of the Gelatin Solutions Ranging from Dilute to Extremely Dilute Concentrations","volume":"50","author":"Yuan","year":"2011","journal-title":"J. Macromol. Sci. Part B Phys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.polymdegradstab.2004.04.024","article-title":"Biodegradation of Type-B Gelatine by Bacteria Isolated from Cinematographic Films. A Viscometric Study","volume":"86","author":"Abrusci","year":"2004","journal-title":"Polym. Degrad. Stab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1529\/biophysj.106.097998","article-title":"Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy","volume":"92","author":"Raub","year":"2007","journal-title":"Biophys. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1016\/j.bpj.2018.04.043","article-title":"The Role of Network Architecture in Collagen Mechanics","volume":"114","author":"Jansen","year":"2018","journal-title":"Biophys. J."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Taufalele, P.V., VanderBurgh, J.A., Mu\u00f1oz, A., Zanotelli, M.R., and Reinhart-King, C.A. (2019). Fiber Alignment Drives Changes in Architectural and Mechanical Features in Collagen Matrices. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0216537"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1364\/BOE.387826","article-title":"Corneal Hydration Assessment Indicator Based on Terahertz Time Domain Spectroscopy","volume":"11","author":"Yao","year":"2020","journal-title":"Biomed. Opt. Express"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0079-6336(01)80003-6","article-title":"Maintaining Corneal Integrity How the \u201cWindow\u201d Stays Clear","volume":"36","author":"Kernacki","year":"2001","journal-title":"Prog. Histochem. Cytochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/BF02869897","article-title":"Thermal Denaturation of Collagen Revisited","volume":"111","author":"Miles","year":"1999","journal-title":"Proc. Indian Acad. Sci. Chem. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.exer.2009.01.010","article-title":"Mechanical anisotropy of porcine cornea and correlation with stromal microstructure","volume":"88","author":"Elsheikh","year":"2009","journal-title":"Exp. Eye Res."}],"container-title":["Biosensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6374\/14\/8\/371\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:26:44Z","timestamp":1760110004000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6374\/14\/8\/371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,30]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["bios14080371"],"URL":"https:\/\/doi.org\/10.3390\/bios14080371","relation":{},"ISSN":["2079-6374"],"issn-type":[{"value":"2079-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,30]]}}}