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Observing Life on a Single-Molecular Scale
Researchers at the Pohang University of Science and Technology have developed a novel method to observe single molecules using a special treatment, followed by tip-enhanced Raman spectroscopy (TERS).

Can single molecules be observed up close, in real-time? Apparently so, according to a team of researchers from the Pohang University of Science and Technology, who have successfully developed a method to observe single molecules at nanometre-scale at room temperature. Interestingly, their method involves the application of a thin insulating layer to the observed molecule, like a protective blanket. The findings of their study were published in Nature Communications.

The team of scientists, with Professor Kyoung-Duck Park and Ph.D. candidate Mingu Kang (Department of Physics) at POSTECH in the lead, together with Professor Yung Doug Suh (Department of Chemistry) at Ulsan National Institute of Science and Technology (UNIST), has managed to observe the arrangement of a single molecule at room temperature, allowing for a better understanding of its structural dynamics.

Prior attempts to observe individual molecules using Raman spectroscopy have proved difficult, as they may react in air and have a wide variety of molecular movements, which makes analysis of their Raman scattering signals difficult. To overcome such limitations, scientists have experimented with extremely low temperatures (below -200 °C) and vacuum environments, but previous attempts have proved inconvenient, with many difficulties faced in the maintenance of the required environmental conditions.

In their attempt to overcome such limitations, the team put one molecule on a surface layered with a thin film of gold, before sandwiching it between a thinner layer of aluminium oxide (Al2O3). This way, the molecule is physically separated from its surroundings, reducing the rates of chemical reaction with air as well as excessive molecular motions.

Consequently, the bound molecule may be observed through tip-enhanced Raman spectroscopy (TERS), which is sensitive enough to provide a nanometre-scale resolution that general optical microscopy fails to provide. This spectroscopy method combines scanning probe microscopy with Raman spectroscopy and is sensitive enough to allow for the detection of the electromagnetic signals produced by one molecule and to be able to discern the heterogeneity in the conformation of the molecule, as well as differentiate whether the molecule was vertically upright or laying flush on the surface.

Mingu Kang of POSTECH mentioned, “Whilst the James Webb Space Telescope can observe the farthest point of the observable universe to reveal the universe’s origin, our nanoscopy for single-molecules observes the smallest unit to reveal the origin of life.” The team’s developed technology and method for observing single molecules have the potential for the investigation of the specific molecular conformation of nanoscale molecules like DNA and proteins with a comparable resolution, which may result in better identification of incurable diseases and hence, more targeted treatments for them.

Source: Kang et al. (2022). Conformational heterogeneity of molecules physisorbed on a gold surface at room temperature.Nature communications,13(1), 1-9.

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