A Dual-Channel Synergistic Ultrasensitive Biosensor for Tumor Liquid Biopsy.

Area of Science:

• Biomedical Engineering
• Molecular Diagnostics
• Oncology

Background:

• Liquid biopsy using circulating tumor DNA (ctDNA) is vital for glioma diagnosis and treatment.
• Low ctDNA abundance and rapid clearance challenge current detection methods like digital PCR and NGS.
• There is a need for highly sensitive and quantitative ctDNA detection techniques.

Purpose of the Study:

• To develop a label-free, dual-channel synergistic detection strategy for ultra-sensitive ctDNA quantification.
• To overcome the limitations of conventional analytical techniques for low-abundance ctDNA detection.
• To validate the biosensor's clinical utility in identifying glioma-specific mutations and providing clinical information.

Main Methods:

• A label-free dual-channel synergistic optical biosensor was designed with structural symmetry breaking and momentum condition regulation.
• A DNA tetrahedron-hybridization chain reaction-gold nanoparticle cascade amplification system was integrated for enhanced sensitivity.
• The biosensor was validated using clinical cerebrospinal fluid samples to detect the IDH1.R132H mutation.

Main Results:

• The dual-channel synergistic biosensor achieved an ultra-low detection limit of 74 zM for ctDNA.
• The platform demonstrated a broad dynamic range spanning 12 orders of magnitude.
• Clinical validation successfully identified the IDH1.R132H mutation in glioma patients using only 1 µL of sample, providing tumor size and staging information.

Conclusions:

• The developed label-free biosensing platform offers rapid, cost-effective, and highly sensitive detection of ctDNA.
• This technology shows significant potential for early cancer screening, molecular diagnostics, and longitudinal disease monitoring in glioma patients.
• The synergistic detection strategy enhances sensing effectiveness, overcoming limitations of conventional methods for low-abundance biomarkers.