Program-Customized Design of MXene-Supported Circuits with Stalker-Regulated DNA Walker for Multiplexed miRNA...

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Diagnostics

Background:

• DNA walkers offer signal amplification in DNA circuits but lack precise control and integration for high-throughput detection.
• Current DNA walker systems face challenges in actuation, movement regulation, and multiplexed detection capabilities.

Purpose of the Study:

• To develop a novel DNA nanomachine, the "DNA stalker", for controlled actuation and regulation of DNA walkers.
• To create an enzyme-free, MXene-supported DNA circuit for multiplexed detection with enhanced signal amplification.
• To enable program-customized fabrication of DNA circuits for flexible detection of various targets, including cancer-related microRNAs (miRNAs).

Main Methods:

• Development of a "DNA stalker" nanomachine that regulates DNA walker movement via target-responsive catalytic hairpin assembly.
• Integration of the DNA stalker and DNA walkers with MXene to create enzyme-free, MXene-supported DNA circuits.
• Utilization of a microfluidic device for simultaneous operation of multiple DNA circuit sets for concurrent miRNA detection.

Main Results:

• The DNA stalker successfully actuated and regulated DNA walker movement, overcoming limitations of existing systems.
• The MXene-supported DNA circuits demonstrated enzyme-free, highly sensitive, and high-throughput detection capabilities.
• Concurrent detection of six miRNAs from human serum samples, distinguishing healthy individuals from cancer patients, was achieved.

Conclusions:

• The developed DNA stalker-based MXene-supported DNA circuits offer a powerful, enzyme-free platform for multiplexed molecular detection.
• This system provides a highly sensitive and high-throughput tool for early clinical diagnosis of cancer through miRNA detection in serum.
• The program-customized design and microfluidic integration pave the way for advanced point-of-care diagnostic tools.