Development of a Self-Viscosity and Temperature-Compensated Technique for Highly Stable and Highly Sensitive...

Area of Science:

• Physics
• Nanotechnology
• Biomedical Engineering

Background:

• Brownian motion is crucial for micro/nanoparticle sizing via optical diffusometry.
• Measurement accuracy is hindered by coupled variations in particle diameter, temperature, and fluid viscosity.
• Janus particles offer a novel approach to separately analyze rotational and translational Brownian motion.

Purpose of the Study:

• To develop a self-compensated diffusometry technique that mitigates temperature and viscosity influences.
• To enable precise micro/nanoparticle characterization and enhance biosensing capabilities.
• To reduce analysis uncertainty in diffusometry measurements.

Main Methods:

• Utilized Janus particles to separately track translational Brownian motion (particle trajectory) and rotational Brownian motion (blinking signal).
• Developed a novel algorithm for self-viscosity and temperature compensation by removing environmental variations.
• Validated the technique through simulations and experiments across a range of temperatures (10-40 °C) and viscosities (1-5 mPa·s).

Main Results:

• Achieved a limit of detection of 0.45 pg/mL for the IFN-γ protein in biosensing applications.
• Demonstrated a 96-fold reduction in viscosity uncertainty and a 15-fold reduction in temperature uncertainty compared to traditional rotational Brownian motion analysis.
• Verified the algorithm's effectiveness in controlled temperature and viscosity environments.

Conclusions:

• The proposed self-compensated diffusometry technique significantly enhances accuracy and reduces uncertainty in micro/nanoparticle measurements.
• This method provides a robust platform for high-sensitivity and high-stability biosensing, particularly for bead-based immunosensing.
• The research offers a promising alternative for advanced analytical techniques requiring ultra-high precision.