Optical forces help reveal how cells communicate

10 Oct 2023

Osaka Metropolitan University detects nanoscale vesicles at low concentrations.

Communication between cells in living systems is a complex process, but known to involve small structures termed vesicles that transport material within and outside the cell.

Nanoscale extracellular vesicles (EVs) come in several different types, but examination of the nucleic acids and proteins they carry can indicate the nature of the cells they came from, making EVs useful biomarkers for their point of origin.

The challenge is to detect these 50 to 150-nanometer EVs rapidly and sensitively from trace samples, so as to potentially open up new understanding of diseases such as cancer and Alzheimer's. Standard assay techniques can identify EVs but not always with the simplicity and speed that clinical testing for these diseases needs.

A project at Japan's Osaka Metropolitan University (OMU) has now developed a new optics-based approach to labeling EVs for detection that is said to significantly improve the sensitivity, precision and detection time in comparison with conventional methods. The study was published in Nanoscale Horizons.

The project utilized laser light to accelerate and control the reaction between nanoscale EVs derived from cancer cells and antibody-modified fluorescent microparticles used as labels, according to OMU. The three-dimensional structure of the resulting aggregates can then analyzed using confocal microscopy.

Using its method, the OMU team could detect 10³ to 10⁴ nanoscale EVs in liquid samples as small as 500 nanoliters within 5 minutes, much more rapidly than measurements using a traditional ultracentrifugation method require.

Early diagnosis of disease

The OMU technique harnesses the optical force produced by a laser to encourage reaction between nanoscale EVs and the fluorescence-labelled microparticle probes.

Under the right conditions and in a bespoke microfluidic channel, optically created pressure can trap the EVs and the probe microparticles at the solid-liquid interface of the channel, and control the binding of the antibody markers to EVs in a way that classical chemical synthesis cannot.

This finely controlled and light-induced assembly of probe particles and nanoscale EVs effectively improves the detection range of the overall analysis, by ensuring that probes are attached more reliably in desired quantities on more of their targets. An enhanced sensitivity can then bring a clearer picture of the role EVs play in biological processes.

"This is an unconventional approach for controlling the detection range of nanoscale extracellular EVs by adjusting the action range and intensity of optical force," commented the project in its published paper. "It significantly increases the sensitivity of detection by over one order of magnitude and reduces the detection time by nearly two orders of magnitude compared to conventional methods."

Speeding up the analysis of nanoscale EVs will overcome a current bottleneck, and be particularly valuable for next-generation liquid biopsy tests in cancer marker detection or other biological applications.

"This research provides a method for ultrafast and ultrasensitive quantitative measurement of biological nanoparticles, offering a foundation for innovative analysis of cell-to-cell communication and early diagnosis of various diseases in the future," commented Takuya Iida of OMU.