Sensight enables quantitative multivariate engineering of high-performance chemical imaging tools

  • Nat Commun. 2026 Jan 27;17(1):2061. doi: 10.1038/s41467-026-68663-2.
Chenglong Wen  1  2 ,  Ying Jiang  1 ,  Tianruo Shen  3 ,  Xuefeng Jiang  1 ,  Shiqi Fan  1 ,  Taorui Yang  1 ,  Xiaogang Liu  3  4 ,  Qiong Luo  5 ,  Xin Li  6  7
Affiliations
  • 1. College of Pharmaceutical Sciences, Women's Hospital School of Medicine, Zhejiang University, Hangzhou, China.
  • 2. State Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing, China.
  • 3. Fluorescence Research Group, Singapore University of Technology and Design, Singapore, Singapore.
  • 4. School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore.
  • 5. College of Pharmaceutical Sciences, Women's Hospital School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
  • 6. College of Pharmaceutical Sciences, Women's Hospital School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
  • 7. State Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing, China. [email protected].
PMID: 41593056 DOI: 10.1038/s41467-026-68663-2
Abstract

Chemical imaging probes enable the visualization of dynamic biology; however, engineering high sensitivity in live cells remains challenging. Here we present Sensight, a quantitative multivariate framework that integrates key photophysical and physicochemical descriptors to predict and optimize probe performance. Using a structurally diverse library, we identify five dominant parameters, define their optimal ranges, and unify them into a radar map representation with strong predictive power and intuitive visualization. This framework extends the structure-activity relationship analysis into imaging sensitivity, capturing complex structure-function relationships that shape probe behavior in live cells. Guided by Sensight, we design G3, a superoxide probe with exceptional sensitivity for detecting early oxidative events. The framework's generality is further demonstrated across distinct systems, including tetrazine-bicyclononyne bioorthogonal chemistry and formaldehyde sensing. Together, these findings establish Sensight as a predictive and generalizable strategy for high-performance probe design, with broad implications for sensing, imaging, and even theranostics.

Products
Inhibitors & Agonists
Other Products