AI-Powered Surface Light Microscopy for In Situ Profiling of Cell Adhesions and Membrane Protein Binding Kinetics
Min Wang1,2, Liangju Li3, Jiying Xu1,2
1Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing100190, China.
Analytical Chemistry
|July 14, 2026
Summary
This study introduces an AI-powered microscopy platform for label-free analysis of membrane protein interactions. It accurately distinguishes real binding events from background noise for precise live-cell kinetic studies.
Area of Science:
- Biophysics
- Cell Biology
- Biosensing
Background:
- Membrane proteins are crucial drug targets, but studying their interactions in situ is challenging.
- Surface plasmon resonance (SPR) imaging offers label-free observation but suffers from background interference.
- Quantitative analysis of molecular interactions at the cell membrane requires overcoming background noise.
Purpose of the Study:
- To develop an AI-powered platform for accurate, label-free quantification of ligand binding to membrane proteins.
- To overcome the limitations of traditional SPR imaging by reducing background noise.
- To enable precise kinetic analysis of molecular interactions at the single live-cell level.
Main Methods:
- Development of an artificial intelligence (AI)-powered surface light microscopy platform.
- Integration of a waveguide sensor chip for dual-channel (scattering and fluorescence) imaging.
- Training an AI model to recognize membrane-associated adhesions in scattering images for signal isolation.
Main Results:
- The AI model achieved an area under the curve of approximately 0.85 in recognizing membrane-associated adhesions.
- The platform successfully isolated real-time ligand-binding signals from nonspecific background.
- Robust in situ binding kinetic analysis at the single live-cell level was enabled.
Conclusions:
- The AI-powered platform transforms label-free biosensing from qualitative to quantitative.
- This method decouples measurement sensitivity from biological interpretation specificity.
- The technology enables molecularly precise analysis directly on live cells, advancing drug development and biological studies.


