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Its abnormal alterations under pathological conditions, such as oxidative stress are closely linked to metabolic diseases and tumors. Capturing these subtle dynamics to reveal connections with organelle dysfunction remains a critical challenge. Existing traditional physical approaches are complex and cannot achieve real\u2010time spatial imaging. Fluorescent probes for polarity sensing could provide spatiotemporal resolution, nevertheless, suffer from unstable signals due to nonfixed dual channels, narrow response ranges, interference from viscosity, and nonlinear responses, hindering quantitative monitoring. We designed an ER\u2010targeted probe\n                    <jats:bold>MBDP<\/jats:bold>\n                    via hybridizing coumarin and BODIPY fluorophores, by introducing a benzene to reduce dihedral angles and a methyl group to inhibit intramolecular rotation, enabling specific polarity response. It shows a broad linear response, strong anti\u2010interference ability, which quantifies ER micro\u2010polarity via dual\u2010channel and lambda mode imaging. It captures ER micro\u2010polarity changes under stress and hippocampal regional differences. Moreover, the remarkable lifetime variations upon polarity change endow\n                    <jats:bold>MBDP<\/jats:bold>\n                    capability under fluorescence lifetime imaging microscope (FLIM). This probe provides a powerful tool with ratiometric imaging and FLIM dual\u2010modal monitoring for ER micro\u2010polarity, aiding in revealing ER\u2010related physiological\/pathological mechanisms and disease research.\n                  <\/jats:p>","DOI":"10.1002\/chem.202502898","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T05:55:37Z","timestamp":1764395737000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A BODIPY\/Coumarin Hybrid Probe for Dual\u2010Mode Fluorescent\/FLIM Imaging of Endoplasmic Reticulum Micro\u2010Polarity"],"prefix":"10.1002","volume":"32","author":[{"given":"Wei","family":"Li","sequence":"first","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Biomedical Functional Materials Nanjing Drum Tower Hospital College of Chemistry and Materials Science Nanjing Normal University  Nanjing 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Nanjing University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Pharmacy Changzhou University  Changzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuncong","family":"Chen","sequence":"additional","affiliation":[{"name":"Chemistry and Biomedicine Innovation Center (ChemBIC) State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical Engineering Nanjing University  Nanjing China"},{"name":"Department of Cardiothoracic Surgery Nanjing Drum Tower Hospital Medical School Nanjing University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-0525","authenticated-orcid":false,"given":"Zhi","family":"Su","sequence":"additional","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Biomedical Functional Materials Nanjing Drum Tower Hospital College of 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