Single molecules, imaging, tracking, and the diffraction limit for finite photons

Since Robert Hooke’s first description of a cell in Micrographia 350 years ago, microscopy has played an important role in understanding the rules of life. Far-field fluorescence microscopy is a powerful approach in biological and biomedical research due to its live cell compatibility and molecular specificity. A major hurdle over the last century has been the limited resolution due to the diffraction of light. Super-resolution microscopy methods, such as single-molecule localization microscopy, overcome this fundamental barrier to improve the resolution limit (250-600 nm, lateral-axial) down to a few nanometers. I will discuss some of our most recent projects which explore newly available sensors/devices, analytical methods and unconventional system instrumentation to allow single molecule imaging and tracking down to a few nanometer precision in live cells and deep tissues. I will show the capabilities of these new imaging systems and analysis pipelines in revealing the fine details of subcellular/tissue features from a diverse set of biological systems including viruses, bacteria, yeasts, mammalian cells and brain sections. Finally, if time permits, I will discuss our recent theoretical work on a new diffraction limit with finite photons.

Single molecules, imaging, tracking, and the diffraction limit for finite photons

Since Robert Hooke’s first description of a cell in Micrographia 350 years ago, microscopy has played an important role in understanding the rules of life. Far-field fluorescence microscopy is a powerful approach in biological and biomedical research due to its live cell compatibility and molecular specificity. A major hurdle over the last century has been the limited resolution due to the diffraction of light. Super-resolution microscopy methods, such as single-molecule localization microscopy, overcome this fundamental barrier to improve the resolution limit (250-600 nm, lateral-axial) down to a few nanometers. I will discuss some of our most recent projects which explore newly available sensors/devices, analytical methods and unconventional system instrumentation to allow single molecule imaging and tracking down to a few nanometer precision in live cells and deep tissues. I will show the capabilities of these new imaging systems and analysis pipelines in revealing the fine details of subcellular/tissue features from a diverse set of biological systems including viruses, bacteria, yeasts, mammalian cells and brain sections. Finally, if time permits, I will discuss our recent theoretical work on a new diffraction limit with finite photons.