Label-free light scattering imaging with purified Brownian motion differentiates small extracellular vesicles in cell microenvironments

Tiny particles called small extracellular vesicles (sEVs) hold immense potential for revolutionizing diagnostics and treatments. These minuscule biological nanoparticles play crucial roles in cellular communication and have applications ranging from disease diagnosis to drug delivery. However, accurately tracking individual sEVs in complex cellular environments has posed a significant challenge—until now.

A groundbreaking study has introduced a novel approach for analyzing sEVs without the need for traditional labeling techniques. Leveraging advanced dark-field technology, researchers at Shandong University have developed a label-free method known as nanoparticle diffusion analysis (NDA). Unlike conventional methods such as nanoparticle tracking analysis (NTA), which rely on fluorescent labeling, NDA harnesses the power of light scattering to track the movement of individual nanoparticles with unparalleled precision.

The key innovation lies in the ability of NDA to determine the diffusion probabilities of single nanoparticles—a feat previously unattainable without biolabeling. By analyzing the purified Brownian motion (pBM) of nanoparticles, researchers can accurately determine their size, even within the complex microenvironments of living cells.

In a series of experiments, the researchers demonstrated the effectiveness of their approach in accurately sizing nanoparticles ranging from 41 to 120 nanometers in diameter. Notably, they achieved consistent size estimations for sEVs derived from both normal and cancerous plasma samples, revealing a statistically significant difference in size between the two.

Moreover, by analyzing the velocity and diffusion coefficient of nanoparticles in cancerous cell microenvironments, the researchers uncovered key parameters for determining their diffusion types—a crucial step in understanding their behavior and potential applications in biomedicine.

This innovative light scattering-based NDA and pBM method not only offers a powerful tool for size determination of nanoparticles but also opens up new possibilities for analyzing sEVs in various biomedical contexts. From diagnosing diseases to delivering targeted therapies, the ability to accurately track and analyze sEVs without the need for labeling represents a significant step forward in the field of nanomedicine.

As researchers continue to explore the potential of sEVs in biomedical applications, tools like NDA promise to play a pivotal role in unlocking their full potential. With further refinement and application, this groundbreaking technology holds the promise of revolutionizing how we diagnose, treat, and understand a wide range of diseases.

Mohamed NA, Wang Z, Liu Q, Chen P, Su X. (2024) Label-Free Light Scattering Imaging with Purified Brownian Motion Differentiates Small Extracellular Vesicles in Cell Microenvironments. Anal Chem [Epub ahead of print]. [abstract]

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