[Developing a novel strategy to enable the observation and analysis at the single-molecular level]

To unlock the secrets of life, enhance our health, and perhaps even overcome aging and death, scientists must be able to selectively observe complex chemical and biological processes at the single-molecular level which will provide insights into the unique properties of each molecules and the dynamics ‘as a function of time and space’. Surface-enhanced Raman spectroscopy (SERS)—a technique that enhances Raman scattering of molecules—has shown exciting potential when compared to ensemble techniques. In other words, SERS may enable compelling opportunities to explore the processes at the single-molecular level.

However, anyone who has used a common optical microscope can attest to the importance of locating the specimen at just the right spot so that the user can see the relevant image magnified through the eyepiece. Compound this importance to the molecular level and the inherent challenge is clear: Although SERS is capable of reporting molecular information at such a level, locating and securing the analyte in the ‘hot spot’ has proven to be a staunch obstacle.

Collaborative research led by Professors Kimoon Kim (Director of the Center for Self-assembly and Complexity, Institute for Basic Science) from the Department of Chemistry (POSTECH), Martin Moskovits (Department of Chemistry and Biochemistry, University of California, Santa Barbara), and Dr. Kangkyun Baek (Team leader of Center for Self-assembly and Complexity, Institute for Basic Science) has have demonstrated a novel strategy for overcoming the aforementioned obstacle by generating “smart” SERS hot spots within a plasmonic nanojunction by utilizing cucurbituril molecules. This achievement was published in the preeminent Journal of the American Chemical Society, and highlighted as a supplementary cover.

The team used cucurbituril—a molecule shaped like a hollow pumpkin—as both a ‘molecular spacer’ to effectively create a nanogap between the silver nanoparticle and substrate and a ‘binding pocket’ to secure the target molecule through strong host-guest interactions. Furthermore, by utilizing spermine—a molecule with a high affinity for the cucurbituril molecule—as a ‘chaperone molecule’, the team was able to accurately and precisely control the position of the target molecule by adjusting the length of polymethylene linkers between the spermine and analyte. In other words, the team was able to create a “smart” SERS hot spot where the cucurbituril acts as both an anchor and a dock.

This achievement is made even more noteworthy because of the relative simplicity and elegance of the platform when compared with the existing methods. Professor Kim anticipates that this platform, coupled with more advanced techniques such as ultrafast SERS with pico- and femtosecond time resolution, will bring forth novel applications that will enable in-depth analysis on the kinetics of individual molecules, including the folding behavior of small proteins and RNA.

This research was supported by the Institute of Basic Science (IBS-R007-D1).