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In Situ Electrical Monitoring of Methylated DNA Based on Its Conformational Change to G-Quadruplex Using a
Yeji Kim1, Yuuki Inoue1, Hijiri Hasegawa1
1Advanced Technology Research Dept., LG Japan Lab Inc., Glass Cube Shinagawa, 4-13-14 Higashi Shinagawa, Shinagawa-ku, Tokyo 140-0002, Japan.
Analytical Chemistry
|December 3, 2021
Summary
This study introduces a novel method for detecting methylated DNA, a key cancer biomarker, using a G-quadruplex conformation transition detected by a solution-gated field-effect transistor (SG-FET). This approach offers a simpler, faster alternative to traditional sequencing methods for early cancer detection.
Area of Science:
- Biomolecular Engineering
- Nanotechnology
- Molecular Diagnostics
Background:
- Methylated DNA is a crucial biomarker for diagnosing and predicting early-stage cancers.
- Current gold-standard methods like sodium bisulfite sequencing are complex, time-consuming, and labor-intensive.
- There is a need for simpler, more reliable methods to detect DNA methylation.
Purpose of the Study:
- To develop a direct and simple method for detecting DNA methylation without labeled materials.
- To utilize the conformational transition of methylated DNA to G-quadruplex structures for detection.
- To employ a solution-gated field-effect transistor (SG-FET) biosensor for sensitive electrical signal generation.
Main Methods:
- A solution-gated field-effect transistor (SG-FET) sensor was developed for label-free DNA methylation detection.
- The sensor leverages the G-quadruplex conformational transition of methylated DNA sequences (e.g., in the BCL-2 gene) in response to K+ concentration.
- Surface-initiated atom transfer radical polymerization was used to graft a dense hydrophilic polymer brush onto the SG-FET surface to minimize electrical noise and control signal detection.
Main Results:
- The SG-FET sensor successfully detected DNA methylation through G-quadruplex formation, generating significant electrical signals.
- The polymer brush effectively reduced nonspecific adsorption, enhancing the signal-to-noise ratio.
- Control over polymer brush thickness allowed for detection of DNA molecular charges within the diffusion layer, adhering to Debye length principles.
Conclusions:
- A novel, label-free method for detecting methylated DNA using SG-FET and G-quadruplex conformation transition has been established.
- The developed platform offers a simple, rapid, and sensitive approach for *in situ* monitoring of DNA methylation.
- This technology has the potential to be developed into a point-of-care device for early cancer diagnostics, eliminating the need for bisulfite conversion and PCR.
