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Understanding and preventing signal drift in continuous biosensors

31 oktober 2025

On October 30, Sebastian Cajigas successfully defended his PhD dissertation at the Department of Biomedical Engineering. His research focused on understanding and preventing long-term signal changes in Biosensing by Particle Motion (BPM) sensors — a promising technology for continuous biomolecular monitoring.

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Photo by Angeline Swinkels

Continuous biosensors measure biomolecules in real time and have the potential to transform healthcare through early diagnosis, personalized treatment, and improved disease management. They can also support industrial process control, environmental monitoring, and biological research. Sebastian Cajigas’ research focused on understanding why these sensors lose sensitivity over time and on strategies to improve their long-term stability.

In his dissertation, Cajigas investigated Biosensing by Particle Motion (BPM), a technology that tracks microscopic particles interacting with a sensing surface. Each binding event changes the particle’s motion, allowing detection of even single molecules. BPM’s single-molecule sensitivity makes it a powerful tool for continuous biomolecular monitoring.

Like all measurement devices, BPM sensors gradually lose sensitivity over time. This signal drift limits their use in applications requiring stable, long-term monitoring, such as tracking stress hormones, drug levels, or disease biomarkers.

Main findings

Cajigas systematically studied how both particles and the sensing surface change during extended operation. Long-term and temperature-controlled experiments revealed the molecular mechanisms responsible for signal drift.

Key findings include:

  • Both functionalized particles and the sensing surface undergo gradual changes, leading to shifts in measured signals.
  • Particle aging, surface degradation, and analyte-independent interactions were separated and characterized.
  • Temperature-accelerated aging allows prediction of long-term performance in shorter experiments.
  • Locked nucleic acid (LNA) surface functionalization improves stability compared to traditional coatings.

These results provide a molecular-level understanding of signal drift and guide the design of more reliable BPM sensors.

Experimental approach and methodological insights

Cajigas studied BPM performance under various conditions: absence of target molecules, exposure to real analytes such as cortisol and glycoalkaloids, and different temperatures.

By isolating each factor, he determined which processes dominate signal changes under specific conditions. The approach also showed that optimizing both particle and surface stability is essential. Temperature-accelerated aging proved useful for estimating sensor lifetime without weeks-long continuous testing.

Challenges

Despite progress, continuous biosensing faces several challenges:

  • Maintaining long-term signal stability remains difficult.
  • Developing robust surface chemistries is crucial for extended operation in complex environments.
  • Translating laboratory systems to real-world applications requires stable materials, optimized analysis, and standardized testing protocols.

Conclusion

Cajigas’ dissertation identifies the molecular mechanisms behind signal drift in BPM sensors and explores strategies to improve long-term stability. His work advances BPM technology and provides approaches applicable across biosensing platforms. These insights bring continuous monitoring technologies closer to real-world use in healthcare, environmental sensing, and industrial applications.

  • Supervisors

    Menno Prins (Promotor), Arthur de Jong (Co-Promotor, Department of Applied Physics & Science Education), and Junhong Yan (Co-Promotor, Helia Biomonitoring)

Media contact

Mira Slothouber
(Communications Advisor)

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