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Here, we report a polarization-controlled intensity-modulated SPR imaging (SPRi) system integrated with a 12-channel microfluidic chip to address these limitations. The working mechanism exploits the phase difference between s- and p-polarized light upon SPR excitation: p-polarized light induces SPR with an additional phase shift, whereas s-polarized light does not participate, converting incident linearly polarized light into elliptically polarized light. By incorporating a polarizer, a quarter-wave plate, and an analyzer, refractive index (RI) changes are transduced into multistage amplified signals: from phase difference to polarization state variation and finally to light intensity change, thereby significantly enhancing the sensitivity. The system achieves an RI sensitivity of 24,300 \u00b1 426 au\/RIU over the linear range of 1.337\u20131.370 RIU, a resolution of (9.96 \u00b1 0.32)\u00d710\u20137 RIU across a dynamic range of 1.331\u20131.410 RIU, and a baseline drift of 0.63 \u00b1 0.02 RU\/min (1 RU = 10\u20136 RIU). Real-time self-referencing effectively suppresses noise, yielding an RMS value of 0.0242. Biomolecular assays demonstrate a sensitivity of 0.06586 au\/(\u03bcg\/mL) for mouse immunoglobulin G (IgG) and a detection limit of 1.56 pg\/mL for D-biotin. This platform offers a robust solution for high-throughput applications in biomedicine, environmental monitoring, and pharmaceutical development.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c02830","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T20:14:28Z","timestamp":1784060068000},"page":"21762-21769","source":"Crossref","is-referenced-by-count":0,"title":["A Wide Dynamic-Range Polarization-Controlled SPR Imaging\nMethod for High-Throughput Biomolecular Detection"],"prefix":"10.1021","volume":"98","author":[{"given":"Chu","family":"Yi","sequence":"first","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510220"]},{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhao","family":"Liang","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510220"]},{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinming","family":"Yuan","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510220"]},{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510220"]},{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Liu","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]},{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6392-8920","authenticated-orcid":true,"given":"Shiqi","family":"Hu","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]},{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]},{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilei","family":"Ding","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]},{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wen","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunqi","family":"Mai","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7067-6562","authenticated-orcid":true,"given":"Yaofei","family":"Chen","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2507-4092","authenticated-orcid":true,"given":"Gui-Shi","family":"Liu","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510220"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]},{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhan","family":"Luo","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510220"]},{"name":"Jinan University , , ,","place":["Guangzhou, P. R. China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"issue":"8","key":"2026072808072306800_cit1","doi-asserted-by":"publisher","first-page":"i","DOI":"10.1016\/0956-5663(95)96965-2","article-title":"Biosensing with surface plasmon resonance--how\nit all started","volume":"10","author":"Liedberg","year":"1995","journal-title":"Biosens. Bioelectron."},{"issue":"2","key":"2026072808072306800_cit2","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1021\/cr068107d","article-title":"Surface plasmon\nresonance sensors for detection of chemical and biological species","volume":"108","author":"Homola","year":"2008","journal-title":"Chem. Rev."},{"key":"2026072808072306800_cit3","doi-asserted-by":"publisher","first-page":"139614","DOI":"10.1016\/j.snb.2026.139614","article-title":"A highly sensitive and temperature-compensated near-infrared\nplasmonic biosensing platform for label-free isothermal nucleic-acid\namplification","volume":"455","author":"Hu","year":"2026","journal-title":"Sens. Actuators, B: Chem."},{"issue":"1","key":"2026072808072306800_cit4","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.snb.2010.05.061","article-title":"On the application\nof gold based SPR sensors for the detection of hazardous gases","volume":"149","author":"Nooke","year":"2010","journal-title":"Sens. Actuators, B: Chem."},{"issue":"8","key":"2026072808072306800_cit5","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1080\/10408398.2021.1958745","article-title":"Recent advances in Surface Plasmon Resonance (SPR)\nbiosensors for food analysis: A review","volume":"63","author":"Ravindran","year":"2023","journal-title":"Crit.\nRev. Food Sci. Nutr."},{"key":"2026072808072306800_cit6","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.snb.2014.11.134","article-title":"Investigation of phase SPR biosensor\nfor efficient\ntargeted drug screening with high sensitivity and stability","volume":"209","author":"Wang","year":"2015","journal-title":"Sens. Actuators, B: Chem."},{"key":"2026072808072306800_cit7","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.bios.2017.03.008","article-title":"Bioelectronics.\nUltra-high sensitivity of the non-immunological affinity of graphene\noxide-peptide-based surface plasmon resonance biosensors to detect\nhuman chorionic gonadotropin","volume":"94","author":"Chiu","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"2026072808072306800_cit8","doi-asserted-by":"publisher","first-page":"133920","DOI":"10.1016\/j.snb.2023.133920","article-title":"Multichannel microfluidic\nvirus sensor for rapid detection of respiratory\nviruses using virus-imprinted polymer for digital livestock farming","volume":"389","author":"Khan","year":"2023","journal-title":"Sens. Actuators, B: Chem."},{"key":"2026072808072306800_cit9","doi-asserted-by":"publisher","first-page":"138149","DOI":"10.1016\/j.snb.2025.138149","article-title":"Integrated\nMulti-channel Microfluidic Biosensing Chip Based on Chain Amplified\nEnhanced Fluorescence for Determination of SEs","volume":"442","author":"Wang","year":"2025","journal-title":"Sens. Actuators, B: Chem."},{"issue":"2","key":"2026072808072306800_cit10","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1109\/JSEN.2021.3133007","article-title":"Recent Advances in Two-Dimensional\nMaterials-Based Kretschmann Configuration for SPR Sensors: A Review","volume":"22","author":"Pandey","year":"2022","journal-title":"IEEE Sens. J."},{"key":"2026072808072306800_cit11","doi-asserted-by":"publisher","first-page":"134897","DOI":"10.1016\/j.snb.2023.134897","article-title":"Quantitatively sensitive and resolution-enhancing\nstrategies in optical signal conversion of SPR images using extensive\nangle-scanning and image-reconstruction","volume":"400","author":"Lee","year":"2024","journal-title":"Sens.\nActuators, B: Chem."},{"issue":"3","key":"2026072808072306800_cit12","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s00604-011-0726-9","article-title":"SPR imaging biosensor for podoplanin: sensor development\nand application to biological materials","volume":"176","author":"Gorodkiewicz","year":"2012","journal-title":"Microchim.\nActa"},{"key":"2026072808072306800_cit13","doi-asserted-by":"publisher","first-page":"117846","DOI":"10.1016\/j.bios.2025.117846","article-title":"Algorithm\nassisted comprehensive optimization of SPR\nsensors towards single molecule detection","volume":"289","author":"Liu","year":"2025","journal-title":"Biosens.\nBioelectron."},{"issue":"1\u20133","key":"2026072808072306800_cit14","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/S0925-4005(98)00208-1","article-title":"Novel polarization\ncontrol scheme for spectral surface\nplasmon resonance sensors","volume":"51","author":"Homola","year":"1998","journal-title":"Sens. Actuators B:\nChem."},{"key":"2026072808072306800_cit15","doi-asserted-by":"publisher","first-page":"133284","DOI":"10.1016\/j.snb.2022.133284","article-title":"Universal\nand flexible design for high-sensitivity\nand wide-ranging surface plasmon resonance sensors based on a three-dimensional\ntuning hypersurface","volume":"380","author":"Hu","year":"2023","journal-title":"Sens. Actuators B: Chem."},{"key":"2026072808072306800_cit16","doi-asserted-by":"publisher","first-page":"136512","DOI":"10.1016\/j.snb.2024.136512","article-title":"A versatile\napproach to quality control of protein-based\nreceptor layers by reversible, nonspecific staining for multiplex\nSPRi immunosensing","volume":"421","author":"Karon\u0301","year":"2024","journal-title":"Sens. Actuators, B: Chem."},{"key":"2026072808072306800_cit17","doi-asserted-by":"publisher","first-page":"129816","DOI":"10.1016\/j.talanta.2026.129816","article-title":"A low-cost,\nLED-based SPRi platform with adaptive spectral analysis and localized\nenrichment for ultrasensitive detection of Tau","volume":"307","author":"Zeng","year":"2026","journal-title":"Talanta"},{"key":"2026072808072306800_cit18","doi-asserted-by":"publisher","first-page":"129172","DOI":"10.1016\/j.talanta.2025.129172","article-title":"Development of a novel SPRi carboxymethyl\ndextran biosensor for sensitive detection of ghrelin in biological\nsamples","volume":"300","author":"Grabia-Lis","year":"2026","journal-title":"Talanta"},{"key":"2026072808072306800_cit19","doi-asserted-by":"publisher","first-page":"114889","DOI":"10.1016\/j.optlastec.2026.114889","article-title":"Advances in\nSPRi sensors: Enhancing performance for small-molecule detection","volume":"198","author":"Chen","year":"2026","journal-title":"Opt. Laser Technol."},{"issue":"9","key":"2026072808072306800_cit20","doi-asserted-by":"publisher","first-page":"094402","DOI":"10.1117\/1.oe.51.9.094402","article-title":"Contrast-enhancing\npolarization control method for surface plasmon imaging sensor","volume":"51","author":"Huang","year":"2012","journal-title":"Opt. Eng."},{"issue":"104","key":"2026072808072306800_cit21","doi-asserted-by":"publisher","first-page":"60227","DOI":"10.1039\/C4RA10501J","article-title":"Highly\nsensitive detection of sulfadimidine in water and dairy products by\nmeans of an evanescent wave optical biosensor","volume":"4","author":"Liu","year":"2014","journal-title":"RSC Adv."},{"key":"2026072808072306800_cit22","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.bios.2015.06.003","article-title":"Triple functional\nDNA\u2013protein\nconjugates: Signal probes for Pb2+ using evanescent wave-induced emission","volume":"74","author":"Wang","year":"2015","journal-title":"Biosens. Bioelectron."},{"issue":"6","key":"2026072808072306800_cit23","doi-asserted-by":"publisher","first-page":"9216","DOI":"10.1109\/jsen.2025.3536976","article-title":"Design and optimization of a highly\nsensitive surface plasmon resonance biosensor for accurate detection\nof mycobacterium tuberculosis","volume":"25","author":"Prava Mondal","year":"2025","journal-title":"IEEE Sens. J."},{"issue":"6","key":"2026072808072306800_cit24","doi-asserted-by":"publisher","first-page":"7671","DOI":"10.1109\/JSEN.2024.3355766","article-title":"Design and simulation\nof SPR sensors by employing silicon and silicon-nitride with mono\nand bimetal layers for sensitivity enhancement","volume":"24","author":"Kumar","year":"2024","journal-title":"IEEE Sens. J."},{"issue":"6","key":"2026072808072306800_cit25","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.3390\/s20061616","article-title":"Surface plasmon resonance-based\nsensing\nutilizing spatial phase modulation in an imaging interferometer","volume":"20","author":"Kan\u030cok","year":"2020","journal-title":"Sensors"},{"issue":"22","key":"2026072808072306800_cit26","doi-asserted-by":"publisher","first-page":"7615","DOI":"10.3390\/s21227615","article-title":"A simple\nphase-sensitive surface plasmon resonance sensor based on simultaneous\npolarization measurement strategy","volume":"21","author":"Li","year":"2021","journal-title":"Sensors"},{"issue":"14","key":"2026072808072306800_cit27","doi-asserted-by":"publisher","first-page":"22404","DOI":"10.1109\/JSEN.2024.3406639","article-title":"Low crosstalk dual-parameter no-core fiber-based SPR sensor with\ndifferentiated silver film thickness","volume":"24","author":"Yin","year":"2024","journal-title":"IEEE Sens.\nJ."},{"issue":"12","key":"2026072808072306800_cit28","doi-asserted-by":"publisher","first-page":"12477","DOI":"10.1109\/JSEN.2023.3268310","article-title":"Prism SPR Glucose\nSensor Based on Gold Nanoparticle\/Gold Film Coupling Enhanced SPR","volume":"23","author":"Fang","year":"2023","journal-title":"IEEE Sens. J."},{"key":"2026072808072306800_cit29","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.optcom.2017.07.064","article-title":"Dual-channel surface\nplasmon resonance\nrefractive index sensor based on modified hetero-core structure fiber","volume":"403","author":"Liu","year":"2017","journal-title":"Opt. Commun."},{"issue":"1","key":"2026072808072306800_cit30","doi-asserted-by":"publisher","first-page":"12864","DOI":"10.1038\/srep12864","article-title":"Surface plasmon\nresonance biosensor based on smart phone platforms","volume":"5","author":"Liu","year":"2015","journal-title":"Sci. Rep."},{"issue":"1","key":"2026072808072306800_cit31","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/s41377-021-00618-2","article-title":"Ultrasensitive detection\nof endocrine\ndisruptors via superfine plasmonic spectral combs","volume":"10","author":"Liu","year":"2021","journal-title":"Light:Sci. Appl."},{"key":"2026072808072306800_cit32","doi-asserted-by":"publisher","first-page":"134335","DOI":"10.1016\/j.snb.2023.134335","article-title":"Optical\nfiber SPR biosensor with frequency multiplexing compensated laser\nheterodyne feedback for ultrasensitive detection of fluoroquinolones","volume":"393","author":"Dai","year":"2023","journal-title":"Sens. Actuators, B: Chem."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c02830","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/29\/21762\/65923108\/acs.analchem.6c02830.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/29\/21762\/65923108\/acs.analchem.6c02830.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:21:25Z","timestamp":1785241285000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/29\/21762\/5208890\/A-Wide-Dynamic-Range-Polarization-Controlled-SPR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":32,"journal-issue":{"issue":"29","published-online":{"date-parts":[[2026,7,14]]},"published-print":{"date-parts":[[2026,7,28]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c02830","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]}}}