SBIR Phase II: Real-time Active Image Stabilization for Microscopy

This Small Business Innovation Research (SBIR) Phase II project will develop and commercialize an integrated system to actively stabilize an optical microscope to the precision required by today's cutting-edge imaging methods. Microscopy in the biological sciences is undergoing radical advancement on several fronts. "Super-Resolution" (SR) techniques circumvent the diffraction limit on resolution once thought to be insurmountable, and promise the ability to image the structures and processes of cell biology at the molecular level. This will usher in profound advancements in the understanding of the inner-workings of the cell. However, significant interrelated barriers remain in the path towards widespread use of SR techniques: (1) they are technically challenging and (2) expensive to implement; and (3) they place physical demands on the microscope platform it was not designed to meet. Foremost of these demands is that SR methods require control over the movement of the biological sample and the stability of the microscope system with nanometer precision. This commercialized integrated system is designed specifically to address these issues and remove these barriers. It uses a 3-axis, piezo-driven nanopositioning stage to control sample motion and actively maintains the stability of the system using the image as the reference point for this stability. The broader impact/commercial potential of this project lies in making SR methods routinely useful to working biologists. These "game-changing" tools will advance our understanding of the molecular bases of disease pathologies, and enable far more exacting methods aimed at their treatments. The new insights will range from those in molecular virology and the development of safer and more effective vaccines, to the molecular mechanisms of neuronal signaling and learning and memory. In fact, it is hard to imagine an area of cell biology that will not be impacted by these emerging SR techniques. One of the pioneers of these methods has likened them to the Hubble telescope: they enable people to see things they simply could not see before. This analogy goes further: there is only one Hubble telescope, and currently very few SR-capable imaging systems, due to both the technical and economic barriers to their routine use. And while SR methods expose the physical limitations of microscopes in an acute manner, their stability and image acquisition requirements are not unique. Thus, this commercial system will be much more broadly useful: it will also enable focal-stability and molecular tracking at the nanometer-scale for any long-term imaging experiment.