{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T22:28:17Z","timestamp":1778106497931,"version":"3.51.4"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000936","name":"Gordon and Betty Moore Foundation","doi-asserted-by":"publisher","award":["4921"],"award-info":[{"award-number":["4921"]}],"id":[{"id":"10.13039\/100000936","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>The ring-assisted Mach\u2013Zehnder interferometer (RA-MZI) has high sensitivity and fast optical response time, and it has been used as a label-free nanophotonic biosensor. Most RA-MZI-based biosensors, however, require chemical modification of the ring surface to immobilize biomolecules that can interact with target molecules for sensing. Here, we report a novel microfluidic-integrated RA-MZI (\u03bcFRA-MZI) where a microfluidic channel was fabricated right above the photonic ring resonator. \u03bcFRA-MZI allows for direct sample delivery to the RA-MZI without chemical modification of the ring surface and measures shifts in the resonance wavelength induced by the presence of target molecules, enabling label-free detection. In order to optimize the sensitivity of \u03bcFRA-MZI, seven devices were fabricated with varied design parameters, including the gap distance between the ring and the bus waveguide (Gring), the length of the multi-mode interferometer (LMMI), and the length of the directional coupler (LDC). Photonic characterization showed that the device with Gring = 1.2 \u03bcm, LMMI = 15.5 \u03bcm, and LDC = 13.5 \u03bcm exhibited the highest extinction ratio (ER) compared to the other six devices, consistent with the simulation-optimized design. Testing with NaCl solutions of varying concentrations yielded a bulk sensitivity of 11.48 nm\/refractive index unit (RIU) and an ER of 0.41. With the potential to further improve the device\u2019s sensitivity and the ability to detect samples directly in flow without chemical modifications of the ring resonator, \u03bcFRA-MZI will provide a robust and effective approach for label-free biosensing.<\/jats:p>","DOI":"10.3390\/bios15110741","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T12:13:08Z","timestamp":1762258388000},"page":"741","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Microfluidic-Integrated, Ring-Resonator-Assisted Mach\u2013Zehnder Interferometer (\u03bcFRA-MZI) as a Label-Free Nanophotonic Sensor"],"prefix":"10.3390","volume":"15","author":[{"given":"Yunju","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, University of California, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan Glenn","family":"Seutter","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of California, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4035-1684","authenticated-orcid":false,"given":"Zihao","family":"Wang","sequence":"additional","affiliation":[{"name":"Microsystems Engineering, Rochester Institute of Technology, Rochester, NY 14623, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7250-975X","authenticated-orcid":false,"given":"Jiandi","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of California, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1039\/c1lc20231f","article-title":"Sensitive on-chip detection of a protein biomarker in human serum and plasma over an extended dynamic range using silicon photonic microring resonators and sub-micron beads","volume":"11","author":"Luchansky","year":"2011","journal-title":"Lab Chip"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22747","DOI":"10.1364\/OE.18.022747","article-title":"Experimental characterization of a silicon photonic biosensor consisting of two cascaded ring resonators based on the Vernier-effect and introduction of a curve fitting method for an improved detection limit","volume":"18","author":"Claes","year":"2010","journal-title":"Opt. 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