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Inaccurate operation can lead to undesired laser damage to surrounding healthy tissue. Closed\u2010loop feedback approaches have been explored in laser ablation but remain underdeveloped for applications such as pigment removal and bacteria inactivation. Here, we introduce signal\u2010activated precision optical treatment (SPOT), a high\u2010speed closed\u2010loop feedback platform based on diffuse reflectance detection. A dedicated and modulated guidance laser continuously interrogates tissue reflectance, and lock\u2010in detection selectively extracts the guidance laser reflectance while effectively rejecting ambient light interference. This design enables high sensitivity to small contrast differences and sub\u2010microsecond response. We demonstrate automated pigment removal using a nanosecond laser and bacterial inhibition with a blue laser. The SPOT framework is adaptable to other optical signal detection, enabling automated, safer, and more precise laser therapies that minimize damage to healthy tissue.<\/jats:p>","DOI":"10.1002\/jbio.70363","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:47:09Z","timestamp":1789429629000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Automated Optical Treatment Based on Diffuse Reflectance Signals"],"prefix":"10.1002","volume":"19","author":[{"given":"Callum D.","family":"Appel","sequence":"first","affiliation":[{"name":"James Tarpo Jr. and Margaret Tarpo Department of Chemistry Purdue University  West Lafayette Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Carlsen","sequence":"additional","affiliation":[{"name":"James Tarpo Jr. and Margaret Tarpo Department of Chemistry Purdue University  West Lafayette Indiana 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