Optical Resonance Imaging: Diffraction-free Microscopy
For centuries, light microscopy has been the main tool for studying cells under physiological conditions. While optical microscopy can be non-invasive, it has a resolution of 200 nm at best. Electron microscopy, on the other hand, can reveal details from the cellular structure at a resolution of 1 nm – but its inherent limitations prevent the non-invasive and dynamic investigation of cells.
Many outstanding questions in cell biology could be answered if light microscopy provided the 1 nm resolution of electron microscopy. Bridging this gap is the focus of Professor Popescu’s research during his Center appointment. He proposes to develop a novel microscopy approach that borrows a concept from magnetic resonance imaging (MRI). The method is referred to as optical resonance imaging (ORI).
The ORI approach encodes spatial information in gradients of the light’s frequency spectrum rather than the (limited) angular distribution of the scattered light. With samples encoded in this way, reconstruction of the image is not bound by diffraction and can achieve nanometer-scale resolution. For example, if two points separated by 1 nm have a measurable difference in their optical spectrum, then measuring their two different spectra will reveal spatial information with 1 nm resolution. ORI can thus render 3-D, dynamic images of live cells with 1 nm resolution in all dimensions.
Professor Popescu has already been collaborating with Professor Zhi-Pei Liang, a world leader in MRI and an ECE Department colleague. Their collaboration has resulted in two publications on new methods for superresolution imaging, essentially combining novel optical imaging approaches with MRI numerical methods.
By merging the molecular (nanometer) and cellular (micron) scales, ORI will enable completely new knowledge about the machinery of live cells. It will be possible, for example, to correlate molecular-level imaging of complex phenomena (e.g., gene expression, protein folding, motor protein activity) with the behavior of the same cell as a whole. This is the kind of information needed to find new cures for many diseases. This is a high-risk, high-return project that, if successful, will provide a new tool to study pure molecular species as well as inorganic samples.