Background

There is a constant need for methods and tools to study proteins in solution at the single molecule level. There are many single molecule analysis approaches available on the market; however, they rely on labeling or tethering. These two approaches require the addition of exogenous labels or tethers that alter biophysical properties. Other approaches such as cryo‑EM and mass‑spectroscopy take the protein out of the aqueous environment and don’t allow for real time observation.

There needs to be an approach to protein interaction analysis and research that offers real‑time observations of proteins that is scalable and allows for a broad uptake within in industry and academia.

Technology Overview

Researchers at the University of Victoria (UVic) have developed a set of optical tweezers with the ability to hold on to single proteins. These tweezers allow the user to “watch” individual proteins move around in solution, in real‑time. The technology uses intrinsic light scattering through a double-nanohole structure in a thin gold film. When a molecule with a greater refractive index than water crosses the double nanohole, it dielectrically loads the region with an intense local field enhancement. The resulting jump in light transmission is a highly sensitive detector for individual molecules. In addition, it can also be used to trap and manipulate an individual molecule.

Researchers have placed the double nanohole at the end of the optical to remove the requirement of a microscope. This novel fiber‑based approach can be used by easily dipping the fiber tip in a microwell.

Benefits

• High signal-to-noise ratio provides reliable work with individual small molecules (1–10 nm)
• Allows a sample with even a single target molecule; essential for precious low-quantity samples, such as mutation studies
• Safe laser power will not disrupt or damage biological samples

Applications

• Drug development
• Diagnostics
• Proteomics
• Metabolomics