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Here, we report polymer-based optical microresonators (MR) as a surface-functionalizable and biocompatible platform for covalently anchoring biofunctional molecules. Highly spherical and monodisperse polystyrene MR were prepared by inkjet printing and conjugated with guest molecules using Sulfo-SANPAH as a heterobifunctional cross-linker. This strategy enabled the stable surface conjugation of multiple classes of biomolecules, including ovalbumin proteins, IgG antibodies, and polylysine, even after repeated washing. MR retained sharp peaks of the whispering-gallery-mode resonance even after conjugation and immersion in water and a buffer solution, indicating their applicability to biologically relevant environments. Furthermore, IgG-conjugated MR were internalized by macrophage cells without causing visible cellular damage. These results establish polymer microresonators as a promising platform for biofunctional and biocompatible optical probes capable of operating in aqueous and cellular environments.<\/jats:p>","DOI":"10.1021\/acsomega.6c07587","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:01:44Z","timestamp":1790607704000},"page":"61744-61750","source":"Crossref","is-referenced-by-count":0,"title":["Monodisperse Polymer\nOptical Microresonators as a\nVersatile Platform for Protein-Conjugated Biocompatible Optical Probes"],"prefix":"10.1021","volume":"11","author":[{"given":"Honoka","family":"Seki","sequence":"first","affiliation":[{"name":"University of Tsukuba , , 1-1-1 Tennodai , , ,","place":["Tsukuba, Ibaraki, Japan, 305-8573"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kariana K.","family":"Dewi","sequence":"additional","affiliation":[{"name":"University of Tsukuba , , 1-1-1 Tennodai , , ,","place":["Tsukuba, Ibaraki, Japan, 305-8573"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Tsujimoto","sequence":"additional","affiliation":[{"name":"University of Tsukuba , , 1-1-1 Tennodai , , ,","place":["Tsukuba, Ibaraki, Japan, 305-8573"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-307X","authenticated-orcid":true,"given":"Sooyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Kyoto University , , Yoshida-Honmachi , Sakyo-Ku, ,","place":["Kyoto, Japan, 606-8501"]},{"name":"The University of Tokyo , , 7-3-1, Hongo , Bunkyo-Ku, ,","place":["Tokyo, Japan, 113-0033"]},{"name":"Japan Science and Technology Agency , , 4-1-8, Honcho , , ,","place":["Kawaguchi, Saitama, Japan, 332-0012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuma","family":"Kubono","sequence":"additional","affiliation":[{"name":"Kyoto University , , Yoshida-Honmachi , Sakyo-Ku, ,","place":["Kyoto, Japan, 606-8501"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Kyoto University , , Yoshida-Honmachi , Sakyo-Ku, ,","place":["Kyoto, Japan, 606-8501"]},{"name":"The University of Tokyo , , 7-3-1, Hongo , Bunkyo-Ku, ,","place":["Tokyo, Japan, 113-0033"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2166-3730","authenticated-orcid":true,"given":"Yohei","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"University of Tsukuba , , 1-1-1 Tennodai , , ,","place":["Tsukuba, Ibaraki, Japan, 305-8573"]},{"name":"Japan Science and Technology Agency , , 4-1-8, Honcho , , ,","place":["Kawaguchi, Saitama, Japan, 332-0012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3184-4217","authenticated-orcid":true,"given":"Hiroshi","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"University of Tsukuba , , 1-1-1 Tennodai , , ,","place":["Tsukuba, Ibaraki, Japan, 305-8573"]},{"name":"University of Tsukuba , , 1-1-1 Tennodai , , ,","place":["Tsukuba, Ibaraki, Japan, 305-8573"]},{"name":"Japan Science and Technology Agency , , 4-1-8, Honcho , , ,","place":["Kawaguchi, Saitama, Japan, 332-0012"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"2026101315073598600_cit1","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1002\/adom.201500232","article-title":"Advances and Prospects for Whispering\nGallery Mode Microcavities","volume":"3","author":"Yang","year":"2015","journal-title":"Adv. Opt. Mater."},{"key":"2026101315073598600_cit2","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1021\/acs.accounts.3c00084","article-title":"Molecular and Supramolecular\nDesigns of Organic\/Polymeric Micro-photoemitters for Advanced Optical\nand Laser Applications","volume":"56","author":"Yamamoto","year":"2023","journal-title":"Acc. Chem. Res."},{"key":"2026101315073598600_cit3","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1002\/lpor.200910016","article-title":"Spherical\nwhispering-gallery-mode microresonators","volume":"4","author":"Chiasera","year":"2010","journal-title":"Laser\nPhoton. Rev."},{"key":"2026101315073598600_cit4","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/s41566-020-0631-z","article-title":"Monitoring contractility\nin cardiac tissue with cellular resolution using biointegrated microlasers","volume":"14","author":"Schubert","year":"2020","journal-title":"Nat. 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Mater."},{"key":"2026101315073598600_cit8","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1039\/D2CC05597J","article-title":"Degradable\noptical resonators as in situ microprobes for microscopy-based observation\nof enzymatic hydrolysis","volume":"59","author":"Takeuchi","year":"2023","journal-title":"Chem. Commun."},{"key":"2026101315073598600_cit9","doi-asserted-by":"publisher","first-page":"103418","DOI":"10.1016\/j.yofte.2023.103418","article-title":"Large measurement\nrange temperature sensor based on\nWGM and MMI in an offset structure fiber coupler","volume":"80","author":"Wang","year":"2023","journal-title":"Opt. Fiber Technol."},{"key":"2026101315073598600_cit10","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1177\/1747519820973929","article-title":"A highly selective\nfluorescent probe for the sensing of Cu2+ based on the\nhydrolysis of a quinoline-2-carboxylate and its application\nin cell imaging","volume":"45","author":"You","year":"2021","journal-title":"J. Chem. Res."},{"key":"2026101315073598600_cit11","doi-asserted-by":"publisher","first-page":"11983","DOI":"10.1039\/D1NJ01951A","article-title":"A coumarin-based\nreversible fluorescent probe for Cu2+ and S2\u2013 and its applicability in vivo and for organism imaging","volume":"45","author":"Lu","year":"2021","journal-title":"New J. Chem."},{"key":"2026101315073598600_cit12","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41566-026-01882-7","article-title":"Single-atomic-ion detection with plasmon-enhanced whispering-gallery-mode\nmicrolasers","volume":"20","author":"Kashanian","year":"2026","journal-title":"Nat. Photonics"},{"key":"2026101315073598600_cit13","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1038\/nnano.2014.180","article-title":"Single-molecule nucleic\nacid interactions\nmonitored on a label-free microcavity biosensor platform","volume":"9","author":"Baaske","year":"2014","journal-title":"Nat. Nanotechnol."},{"key":"2026101315073598600_cit14","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/nphoton.2015.129","article-title":"Intracellular microlasers","volume":"9","author":"Humar","year":"2015","journal-title":"Nat.\nPhotonics"},{"key":"2026101315073598600_cit15","doi-asserted-by":"publisher","first-page":"5647","DOI":"10.1021\/acs.nanolett.5b02491","article-title":"Lasing\nwithin Live Cells Containing Intracellular Optical Microresonators\nfor Barcode-Type Cell Tagging and Tracking","volume":"15","author":"Schubert","year":"2015","journal-title":"Nano Lett."},{"key":"2026101315073598600_cit16","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1021\/acsphotonics.2c01611","article-title":"Microcavity- and Microlaser-Based Optical Barcoding:\nA Review of Encoding Techniques and Applications","volume":"10","author":"Anwar","year":"2023","journal-title":"ACS Photonics"},{"key":"2026101315073598600_cit17","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/s41566-019-0489-0","article-title":"Wavelength-encoded\nlaser particles for massively multiplexed cell tagging","volume":"13","author":"Martino","year":"2019","journal-title":"Nanophotonics"},{"key":"2026101315073598600_cit18","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1038\/s41598-018-20025-9","article-title":"Silica Gel Coated Spherical Micro resonator for Ultra-High\nSensitivity Detection of Ammonia Gas Concentration in Air","volume":"8","author":"Mallik","year":"2018","journal-title":"Sci. Rep."},{"key":"2026101315073598600_cit19","doi-asserted-by":"publisher","first-page":"111286","DOI":"10.1016\/j.optmat.2021.111286","article-title":"Refractometric gas\nsensing using a whispering gallery mode microresonator coated with\na supra-micron sol-gel layer","volume":"118","author":"Zhivotkov","year":"2021","journal-title":"Opt. Mater."},{"key":"2026101315073598600_cit20","doi-asserted-by":"publisher","first-page":"9317","DOI":"10.3390\/s101009317","article-title":"Bioconjugation strategies for microtoroidal\noptical resonators","volume":"10","author":"Hunt","year":"2010","journal-title":"Sensors"},{"key":"2026101315073598600_cit21","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.biomaterials.2011.09.036","article-title":"Whispering gallery mode biosensor quantification of fibronectin adsorption\nkinetics onto alkylsilane monolayers and interpretation of resultant\ncellular response","volume":"33","author":"Wilson","year":"2012","journal-title":"Biomaterials"},{"key":"2026101315073598600_cit22","doi-asserted-by":"publisher","first-page":"4571","DOI":"10.1021\/acs.jpcc.9b10870","article-title":"Formation of Poly-l-lysine Monolayers\non Silica: Modeling\nand Experimental Studies","volume":"124","author":"Kosior","year":"2020","journal-title":"J. Phys. Chem. C"},{"key":"2026101315073598600_cit23","doi-asserted-by":"publisher","first-page":"3206","DOI":"10.3390\/molecules30153206","article-title":"Surface Functionalization\nof Nanoparticles for Enhanced\nElectrostatic Adsorption of Biomolecules","volume":"30","author":"Gorohovs","year":"2025","journal-title":"Molecules"},{"key":"2026101315073598600_cit24","doi-asserted-by":"publisher","first-page":"130512","DOI":"10.1016\/j.snb.2021.130512","article-title":"Whispering\nGallery Modes-based biosensors for real-time monitoring and binding\ncharacterization of antibody-based cancer immunotherapeutics","volume":"346","author":"Freile","year":"2021","journal-title":"Sens. Actuators B Chem."},{"key":"2026101315073598600_cit25","doi-asserted-by":"publisher","first-page":"2404686","DOI":"10.1002\/adhm.202404686","article-title":"Enhanced PDMS\nFunctionalization for\nOrgan-on-a-Chip Platforms Using Ozone and Sulfo-SANPAH: A Simple Approach\nfor Biomimetic Long-Term Cell Cultures","volume":"14","author":"Pe\u0301rez-Calixto","year":"2025","journal-title":"Adv.\nHealthcare Mater."},{"key":"2026101315073598600_cit26","doi-asserted-by":"publisher","first-page":"5030","DOI":"10.1039\/D5MA00176E","article-title":"Monodisperse and size-modulable spherical\noptical resonators produced from synthetic polymers by inkjet printing\ntoward applications under water","volume":"6","author":"Dewi","year":"2025","journal-title":"Mater. Adv."},{"key":"2026101315073598600_cit27","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.1140\/epjst\/e2014-02247-2","article-title":"Development\nof a fully automated in-vitro diagnostics system based on low-Q whispering\ngallery modes in fluorescent microparticles","volume":"223","author":"Bischler","year":"2014","journal-title":"Eur. Phys. J-Spec. Top"},{"key":"2026101315073598600_cit28","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1364\/AOP.7.000168","article-title":"Whispering gallery\nmode sensors","volume":"7","author":"Foreman","year":"2015","journal-title":"Adv. Opt. Photonics"},{"key":"2026101315073598600_cit29","doi-asserted-by":"publisher","first-page":"55934","DOI":"10.3791\/55934","article-title":"Fabrication\nof Polymer Microspheres for Optical Resonator and Laser Applications","volume":"124","author":"Yamamoto","year":"2017","journal-title":"J. Vis. Exp."},{"key":"2026101315073598600_cit30","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abd1211","article-title":"Environmental exposure enhances the\ninternalization\nof microplastic particles into cells","volume":"6","author":"Ramsperger","year":"2020","journal-title":"Sci. Adv."},{"key":"2026101315073598600_cit31","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1006\/excr.1998.4110","article-title":"Size of\nIgG-opsonized particles determines macrophage response during internalization","volume":"242","author":"Koval","year":"1998","journal-title":"Exp. Cell Res."},{"key":"2026101315073598600_cit32","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1007\/s00436-019-06310-0","article-title":"Increased\nphagocytosis\nand growth inhibition of Encephalitozoon cuniculi by LPS-activated\nJ774A.1 murine macrophages","volume":"118","author":"Gonza\u0301lez-Machorro","year":"2019","journal-title":"Parasitol. Res."},{"key":"2026101315073598600_cit33","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.21769\/BioProtoc.1180","article-title":"Macrophage Inflammatory\nAssay","volume":"4","author":"Bartosh","year":"2014","journal-title":"Bio-Protocol."},{"key":"2026101315073598600_cit34","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1039\/d2en00214k","article-title":"Does size matter? A proteomics-informed comparison\nof the effects of polystyrene beads of different sizes on macrophages","volume":"9","author":"Collin-Faure","year":"2022","journal-title":"Environ. Sci.: Nano"},{"key":"2026101315073598600_cit35","doi-asserted-by":"publisher","first-page":"1092743","DOI":"10.3389\/fimmu.2023.1092743","article-title":"The\ninternal dose makes the poison: higher internalization of polystyrene\nparticles induce increased perturbation of macrophages","volume":"14","author":"Collin-Faure","year":"2023","journal-title":"Front. Immunol."},{"key":"2026101315073598600_cit36","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1038\/s41566-023-01264-3","article-title":"Single-particle\nphotoacoustic vibrational spectroscopy using optical microresonators","volume":"17","author":"Tang","year":"2023","journal-title":"Nat. Photonics"},{"key":"2026101315073598600_cit37","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41377-025-01809-x","article-title":"Large-scale combinatorial\noptical barcoding of cells with laser particles","volume":"14","author":"Martino","year":"2025","journal-title":"Light Sci. Appl."},{"key":"2026101315073598600_cit38","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/s41377-024-01471-9","article-title":"Deformable\nmicrolaser force sensing","volume":"13","author":"Dalaka","year":"2024","journal-title":"Light Sci. Appl."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c07587","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/40\/61744\/68678900\/acsomega.6c07587.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/40\/61744\/68678900\/acsomega.6c07587.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:49:43Z","timestamp":1791920983000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/40\/61744\/5440112\/Monodisperse-Polymer-Optical-Microresonators-as-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":38,"journal-issue":{"issue":"40","published-online":{"date-parts":[[2026,9,28]]},"published-print":{"date-parts":[[2026,10,13]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c07587","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]}}}