Resistive pulse sensing of analyte-induced multicomponent rod aggregation using tunable pores

Area of Science:

• Nanotechnology
• Biophysics
• Analytical Chemistry

Background:

• Resistive pulse sensing is a technique for analyzing particles passing through a pore.
• Distinguishing between different particle shapes, like rods and spheres, is crucial for accurate sensing.
• Current methods may struggle to differentiate complex particle morphologies.

Purpose of the Study:

• To investigate the resistive pulse signal characteristics of rod-shaped nanoparticles.
• To develop a method for distinguishing rod-shaped particles from spheres using resistive pulse sensing.
• To create a novel agglutination assay for sensitive biomolecule detection using rod-shaped nanoparticles.

Main Methods:

• Utilizing tunable pores in elastomeric membranes for resistive pulse sensing.
• Analyzing blockade event magnitude (Δi(p)) for particle size and full width at half maximum (FWHM) duration for particle dynamics.
• Developing surface chemistry and capture ligand strategies for controlled nanoparticle aggregation.

Main Results:

• Rod-shaped nanoparticles exhibit distinct resistive pulse signals compared to spheres, differing in both magnitude and duration.
• Measured FWHM durations were larger than simulated, attributed to varied particle orientations within the pore.
• Demonstrated successful formation of end-on-end and side-on aggregates based on surface chemistry and analyte presence.
• Achieved femtomolar detection limits for platelet-derived growth factor (PDGF-BB) using an aptamer-based assay.

Conclusions:

• Resistive pulse sensing can effectively differentiate rod-shaped nanoparticles from spheres based on unique signal characteristics.
• The orientation-dependent dwell time provides an additional parameter for particle analysis.
• This approach enables the development of advanced agglutination assays for sensitive and potentially multiplexed biomolecule detection.