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Metal-Graphene Hybrid Terahertz Metasurfaces for Circulating Tumor DNA Detection Based on Dual Signal Amplification
Xizi Luo1, Jining Li2, Guorong Huang1
1Department of Laboratory Medicine, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China.
ACS Sensors
|April 11, 2024
Summary
This study introduces a novel metal-graphene hybrid terahertz (THz) metasurface for highly sensitive, enzyme-free detection of circulating tumor DNA (ctDNA) in pancreatic cancer patients. The innovative biosensor achieves subfemtomolar sensitivity and single-nucleotide mismatch selectivity.
Area of Science:
- Terahertz spectroscopy
- Biosensing
- Nanomaterials
Background:
- Terahertz (THz) spectroscopy offers label-free biosensing but faces limitations in clinical settings due to suboptimal detection performance.
- Circulating tumor DNA (ctDNA) is a crucial biomarker for early cancer detection, particularly in pancreatic cancer.
- Existing methods for ctDNA detection often require complex procedures or lack sufficient sensitivity.
Purpose of the Study:
- To develop a sensitive and enzyme-free biosensor for detecting ctDNA in pancreatic cancer plasma.
- To investigate the mechanism of enhanced THz signal transduction using a metal-graphene hybrid metasurface amplified by gold nanoparticles.
- To demonstrate the potential of this THz biosensor for clinical diagnostics and biomarker discrimination.
Main Methods:
- Fabrication of metal-graphene hybrid THz metasurfaces (MSs) integrated with gold nanoparticles (AuNPs).
- Experimental and theoretical investigation of graphene's role in enhancing THz signal transmission through MS resonators.
- Development of a cascade hybridization chain reaction assay for dual signal amplification (chemical and optical) of target ctDNA.
Main Results:
- Achieved subfemtomolar detection sensitivity and single-nucleotide mismatch selectivity for ctDNA.
- Demonstrated a 2-orders-of-magnitude improvement in sensitivity for ctDNA detection compared to previous methods.
- Successfully discriminated between pancreatic cancer patients and healthy individuals based on targeted ctDNA quantification.
Conclusions:
- The developed metal-graphene hybrid THz metasurface biosensor provides a highly sensitive and selective platform for enzyme-free ctDNA detection.
- The synergistic effect of graphene and AuNPs significantly enhances THz signal transduction for improved biosensing performance.
- This approach represents a significant advancement in THz biosensing for clinical applications, enabling early detection and discrimination of pancreatic cancer.

