Single-molecule manipulation and imaging platform

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Macroscopic properties of materials and reagents are governed by molecular-scale interactions. In some fields, subtle details of these interactions can completely change the property of a compound or material. For example, can a new cancer drug be engineered to bind only to the target cell surface receptor, without interrupting other cellular processes? Or, can the water-absorbing properties of an organic nanoparticle be altered to increase its moisture content? Molecular interactions can vary significantly from one molecule to the next, making measurements of averages deceptive and uninformative. We have developed a new technology, named CLiC for "convex lens-induced confinement", to bring simple and inexpensive single-molecule imaging capabilities to microscopy. While single-molecule imaging technologies already exist (TIRF microscopy, optical tweezers), they are cumbersome and their use of 'molecular tethers' biases the reactions they attempt to study. CLiC is much simpler: molecules are mechanically squeezed into tiny glass 'boxes' etched into a glass slide. They can be held indefinitely in the field of view of a microscope, enabling intensive, individual, and unbiased study. ScopeSys, a Canadian startup, is commercializing CLiC and has already sold 5 systems. To prepare CLiC for widespread commercial adoption we will 1) refine CLiC's temperature control and reagent exchange functionality to enable experimentation over a wider range of conditions, 2) develop intuitive analysis software so external users can extract meaningful single-molecule information from their observations, 3) improve the scalability of our 'flow cell', and 4) validate the use of CLiC in several important applications. Success of this work will allow a broad range of Canadian researchers early and easy access to single molecule imaging methods to accelerate their research, even in laboratories with limited funds. In addition, the work will allow ScopeSys to grow as a Canadian company and create high quality jobs for young science and technology professionals.**