Stretch Targets for Microscopy

Researchers have developed an approach for stretching and immobilizing single DNA molecules on glass surfaces, offering enhanced precision for super-resolution imaging. This method, detailed in AIP Advances, uses pressure flow in microchannels combined with chemical surface treatment to overcome limitations in traditional techniques. The approach is set to improve the accuracy of DNA analysis in structural and molecular biology.

The study team addressed a longstanding challenge in DNA imaging: maintaining the molecule's linear structure while minimizing thermal fluctuations that degrade imaging quality. By applying pressure flow in a microchannel, the team achieved controlled stretching of DNA molecules. The unfurled molecules were then immobilized on a glass surface treated with a chemical glue, ensuring stability during imaging. This process allowed for precise control of the DNA stretch ratio, which was adjusted by modulating flow velocity of the liquid.

The researchers then employed a super-resolution imaging method – direct stochastic optical reconstruction microscopy (STORM) – to examine the stretched and immobilized DNA. At a lateral resolution of 80 nm – which is close to theoretical limits – the DNA images confirmed the system's ability to minimize molecular vibrations and thermal drift, common issues in previous methods.

The study highlighted the versatility of this stretching approach for analyzing DNA with varying lengths and structures. Corresponding author Naoli Azuma explained, “While it is not yet possible to directly visualize individual base pairs, these methods enable much higher precision in observing molecular-scale structures.” The study report also proposes integrating the method with cryogenic techniques to enhance imaging stability and resolution.

The research introduces a scalable and precise tool for molecular biology, paving the way for new discoveries in genetic and genomic research. Applications of this technique could include DNA structural studies, protein-DNA interaction mapping, and genome visualization. Future work will focus on refining the process and expanding its use in complex biological systems.