Molecular Origins of Long-Term Changes in a Competitive Continuous Biosensor with Single-Molecule Resolution

Area of Science:

• Biotechnology
• Biosensor technology
• Nanotechnology

Background:

• Particle motion biosensing offers continuous analyte monitoring at low concentrations.
• Long-term signal drift is a significant challenge in current particle motion biosensor systems.
• Understanding the molecular basis of this drift is crucial for sensor improvement.

Purpose of the Study:

• To develop a methodology for elucidating the molecular origins of long-term signal changes in particle motion biosensors.
• To investigate the aging process of individual sensor components (particles and surfaces).
• To analyze changes in particle motion patterns and switching activity over extended periods.

Main Methods:

• Aging experiments were conducted on sensor particles and surfaces independently.
• Analysis of particle motion patterns and switching activity distributions over several days.
• Focus on a competitive sensor design for cortisol detection without flow.

Main Results:

• Identified two primary hypotheses for signal drift: antibody loss and non-specific interactions on particles, and analogue molecule dissociation from the sensing surface.
• Demonstrated how aging affects individual sensor components.
• Revealed population-level changes in particle behavior over time.

Conclusions:

• The developed methodologies provide insights into the molecular degradation mechanisms affecting particle motion biosensors.
• Addressing antibody stability and surface-analyte interactions is key to enhancing sensor operational lifespan.
• This work lays the foundation for developing more robust and long-lasting biosensing devices.