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Reversible Sandwich-Based Particle Nanoswitch for Continuous Protein Monitoring at Picomolar Concentrations with
Claire M S Michielsen1,2, Junhong Yan3, Max H Bergkamp3
1Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, 5612 AZ, The Netherlands.
Angewandte Chemie (International Ed. in English)
|October 21, 2025
Summary
This study introduces a novel particle nanoswitch sensor for continuous, real-time protein monitoring. The sensor achieves sensitive and accurate detection of proteins like lactoferrin at picomolar levels over extended periods.
Area of Science:
- Biotechnology
- Biosensing
- Nanotechnology
Background:
- Continuous protein monitoring is crucial for biological systems and bioprocess control.
- Existing sensors often lack reversibility and long-term accuracy.
- Need for real-time measurement tools in dynamic biological environments.
Purpose of the Study:
- To develop a reversible particle nanoswitch sensor for continuous protein detection.
- To demonstrate the sensor's capability for real-time monitoring of specific proteins.
- To enable long-term, high-accuracy measurements in bioprocesses.
Main Methods:
- Utilized particle nanoswitches with two antibody fragments for reversible protein binding.
- Employed site-specific conjugation for optimal antibody orientation.
- Detected transient sandwich complexes via single-molecule tracking of tethered particles.
Main Results:
- Demonstrated continuous sensing of lactoferrin at picomolar concentrations.
- Achieved a delay time of less than 12 minutes for measurements.
- Maintained accuracy with a mean absolute relative difference below 10% over 12 hours.
Conclusions:
- Developed a novel sensor for rapid, continuous protein detection at low concentrations.
- The reversible nanoswitch enables long-term monitoring of dynamic biological processes.
- This technology advances real-time measurement and control strategies in bioprocessing.
