A CMOS label-free DNA sensor using electrostatic induction of molecular charges

Area of Science:

• Biosensing
• Nanotechnology
• Molecular Diagnostics

Background:

• Label-free biosensors are crucial for real-time detection of biological interactions.
• Existing methods like ion-sensitive field-effect transistors (ISFETs) face limitations in stability and reference electrode choice.
• Direct charge accumulation offers a promising label-free detection strategy.

Purpose of the Study:

• To develop and validate a novel label-free biosensor for DNA hybridization detection.
• To improve signal-to-noise ratio (SNR) and measurement robustness compared to existing technologies.
• To demonstrate the sensor's capability for specific pathogen detection, such as H5N1 avian influenza virus.

Main Methods:

• Utilizes a direct charge accumulation method to measure surface potential on oligonucleotide-modified electrodes.
• Employs an oversampling effect and differential architecture to enhance SNR.
• Fabricated using a 0.35 μm complementary metal-oxide-semiconductor (CMOS) process, integrating electrodes and readout circuits.
• Performs single-base mismatch tests for specificity assessment.

Main Results:

• Achieves a detectable surface potential range of 88.3 dB and a detection limit of 36 μV.
• Demonstrates stable, robust, and reproducible measurements, independent of reference voltage fluctuations.
• Successfully detects specific oligonucleotide sequences from the H5N1 avian influenza virus.
• Establishes a limit of detection of 100 pM for target sequences.

Conclusions:

• The developed label-free biosensor provides a sensitive, stable, and reproducible platform for DNA hybridization detection.
• The CMOS-integrated sensor offers advantages over traditional ISFETs, including wider reference electrode compatibility.
• The sensor's ability to detect H5N1 sequences highlights its potential for infectious disease diagnostics.