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Cell Surface Ion-Seq: Potassium Ion Monitoring in the Colorectal Cancer Cellular Microenvironment Based on Split
Zhiyong Huang1,2, Xuyang Shi3, Yunben Yang1
1Department of Clinical Laboratory, Zhejiang Cancer Hospital, The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, P. R. China.
ACS Central Science
|December 31, 2025
Summary
This study introduces Ion-seq, a novel cell surface biosensor for monitoring potassium (K+) homeostasis at single-cell resolution. This breakthrough enables ionic phenotyping, advancing disease diagnosis and personalized medicine.
Area of Science:
- Biotechnology
- Molecular Biology
- Genomics
Background:
- Potassium ions (K+) are crucial for cellular functions and electrolyte balance.
- Current single-cell sequencing methods face limitations in monitoring ion concentrations due to the small scale of ions.
- Accurate monitoring of K+ homeostasis is vital for understanding electrolyte imbalance symptoms.
Purpose of the Study:
- To develop a novel biosensor for single-cell ion sequencing (Ion-seq) to monitor K+ homeostasis.
- To overcome the limitations of antibody-based detection for subnanometer ions like K+.
- To enable ionic phenotyping at single-cell resolution within heterogeneous cell populations.
Main Methods:
- Utilized a cell surface biosensor employing split G-quadruplex (G4) DNA structures.
- A lipid-labeled capture probe anchored to the cell membrane to detect released K+.
- Sensing probes captured by the membrane-bound probe formed a complete G-quadruplex upon K+ binding, enabling sequencing for monitoring.
Main Results:
- Successfully demonstrated a biosensor for monitoring potassium (K+) homeostasis at single-cell resolution using Ion-seq.
- Enabled the correlation of ionic activity with cellular phenotypes in clinical samples.
- Showcased the potential for analyzing other ions at the single-cell level.
Conclusions:
- Ion-seq provides a powerful tool for monitoring K+ homeostasis and ionic phenotyping in clinical samples.
- This technology advances the understanding of cellular heterogeneity and function in the context of ion dynamics.
- The biosensor platform holds significant potential for disease diagnosis and personalized medicine through single-cell ion analysis.
