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A Multiplexable Plasmonic Hairpin-DNA Sensor Based On Target-specific Tether Dynamics.

Jeanne Elisabeth van Dongen¹, Laurens Rudi Spoelstra¹, Johanna Theodora Wilhelmina Berendsen¹

¹BIOS Lab on a Chip Group, MESA+ & TechMed Institutes, Max Planck Center for Complex Fluid Dynamics, University of Twente, P.O. Box 217 7500 AE Enschede, The Netherlands.

|December 1, 2021

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This study introduces a novel method for multiplexed DNA sensing using hairpin-based single-molecule sensors. The approach enhances multiplexing capabilities by designing DNA tethers with distinct dynamics for sensitive biomarker detection.

Area of Science:

Biomarker detection
Single-molecule sensing
Nanotechnology

Background:

Current multiplexed sensing technologies for simultaneous biomarker measurement at subnanomolar concentrations face challenges in complexity and read-out.
High sensitivity, specificity, precision, and accuracy are critical for advanced diagnostic and research applications.

Purpose of the Study:

To develop a novel, simplified approach for multiplexed sensing using hairpin-based single-DNA molecule sensors.
To overcome the limitations of existing multiplexing strategies in single-molecule sensor systems.

Main Methods:

Design of target-dependent single-stranded DNA (ssDNA) hairpins to create DNA tethers with distinct dynamics upon target binding.
Utilizing a numerical model to demonstrate that varying the stem length of the ssDNA hairpin results in significantly different dynamic tether behaviors.

Keywords:

biosensors multiplexing nanoplasmonics single-molecule sensing tethered-particle motion

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Employing the distance-dependent coupling of gold nanoparticles (AuNPs) to gold films for probing z-axis dynamic behavior with laser microscopy.

Main Results:

The proposed hairpin design enables distinct dynamic tether behaviors correlated with specific target binding.
Numerical modeling confirms that ssDNA hairpin stem length is a key factor in differentiating dynamic tether responses.
The distance-dependent coupling of AuNPs to gold films provides a viable method for detecting these dynamic changes.

Conclusions:

This novel hairpin-based approach offers a simplified and effective strategy for multiplexed single-DNA molecule sensing.
The method allows for sensitive and specific detection of multiple biomarkers by exploiting unique DNA tether dynamics.
The technique holds promise for advancing high-sensitivity multiplexed biomarker measurements in various scientific and diagnostic fields.