A generalizable nanopore sensor for highly specific protein detection at single-molecule precision

Area of Science:

• Biophysics
• Molecular Diagnostics
• Nanotechnology

Background:

• Protein detection is crucial for molecular diagnostics, with nanopore technology showing promise.
• Existing nanopore methods face challenges with steric hindrance, limiting specific protein interface implementation.
• Developing specific, sensitive, and architecture-preserving protein detection methods is essential.

Purpose of the Study:

• To engineer a modular nanopore sensor with programmable antibody-mimetic binders for specific protein detection.
• To overcome steric hindrance issues in nanopore-based protein analytics.
• To demonstrate the versatility of this approach for diverse protein analytes.

Main Methods:

• Formulation of sensing elements by fusing programmable antibody-mimetic binders to monomeric protein nanopores.
• Development and validation of nanopore sensors for protein analytes with varying size, charge, and complexity.
• Analysis of unique electrical signatures generated by binder-analyte interactions at the nanopore tip.

Main Results:

• Successful creation of a modular nanopore sensor system.
• Demonstrated detection of diverse protein analytes with high specificity and sensitivity.
• Observed unique electrical signatures correlating with protein identity, quantity, and binding interactions.

Conclusions:

• The programmable binder-nanopore fusion offers a versatile platform for protein detection.
• This modular design preserves nanopore sensor architecture, specificity, and sensitivity.
• The approach provides a foundation for advanced biomarker detection in biofluids for biomedical diagnostics.