Research News by Edwin Cartlidge
Scientists in China and Australia have developed a groundbreaking method using optically trapped nanoparticles to measure minuscule forces in water with high spatial resolution. This innovative technique, which leverages optical astigmatism and neural networks, has the potential to enhance our understanding of protein function and improve disease diagnosis.
Measuring Tiny Forces
Biological processes often involve extremely small forces, such as the tension in DNA molecules and the effort required to organize genetic material in chromosomes, which are less than 10^-12 newtons. While several techniques exist to measure such forces, they all have limitations. For example, microscopy with tiny cantilever arms is sensitive at these levels but struggles to map force distribution in three dimensions.
Photonic force microscopy, a promising technique, uses optical tweezers to hold a tiny dielectric particle in place and collects light scattered off the particle. The interference between scattered and unscattered light reveals the particle’s three-dimensional position and the forces acting on it. However, quantifying these forces in a liquid environment requires accounting for the particle’s buffeting by the liquid’s molecules and measuring shifts in the particle’s fluctuating position distribution center.
Overcoming Thermal Limits
The nanoscale thermal limit has been a significant challenge in force measurements, with the best reported sensitivity being 10 femtonewtons (fN) per square root of the bandwidth, achieved with a 500 nm diameter particle. Smaller particles could improve sensitivity by reducing drag in a liquid, but this comes with challenges such as lower scattering signals and the need for higher trapping power, which generates unwanted heat.
Innovative Approach with Lanthanide-Doped Nanoparticles
Fan Wang and colleagues from Beihang University, China, have addressed these challenges using lanthanide-doped nanoparticles. These particles can be trapped via ion resonance with minimal power and temperature rise. Their fluorescence allows for tracking by detecting their emission, bypassing the problem of insufficient scattering.
The main challenge was to perform force measurements in three dimensions. While achieving high sensitivity in the x and y dimensions is straightforward, the z dimension required a novel approach. The researchers used a cylindrical lens to create optical astigmatism, transforming the emission spread into an ellipse. By recording images at different heights and correlating the z value with the ellipse shape, they achieved precise measurements.
Neural Networks to Enhance Accuracy
To overcome the distortion caused by Brownian motion during calibration, the team employed a neural network. Training the network with various examples of spread functions from different heights allowed it to accurately identify the z position of unknown images. This method consistently limited errors in the z position to less than 30 nm, with x and y errors at just 5 nm.
The team successfully measured forces as low as 0.1 fN by exposing 58-nm-diameter nanoparticles to an external force using electrodes. They also calculated the force exerted on a trapped nanocrystal by a nearby gold surface, finding that coating the gold with DNA reduced the surface force. This suggests that their setup could be used to investigate biomolecular interactions.
Future Prospects
The research opens new avenues for nanoscale thermally limited force sensing and offers opportunities for detecting sub-femtonewton forces over long distances and biomechanical forces at the single-molecule level. The researchers aim to improve sensitivity further by using smaller, brighter nanoparticles and enhancing surface modification for biological sensing.
This breakthrough holds promise for advancing our understanding of molecular interactions and improving diagnostic techniques in medicine.
