How can we construct a high-resolution camera capable of imaging the time-of-arrival, polarisation and wavelength of each of the maximal 10Gphoton/s emitted from a labelled, biological cell?
Such a measurement would capture the complete information available in the optical signal, and significantly enhance our ability to observe the organisation, movement and interactions of cellular components at molecular scales. Advances in single molecule light microscopy are steadily improving our understanding of the processes underlying normal cellular function, and their alteration in disease states. However, these technologies are unable to reach their full potential due to their reliance on pre-existing, suboptimal detectors. A dedicated camera technology is now required to permit simultaneous, multidimensional measurements of large cohorts of molecules at high temporal and spatial (sub-diffraction limit) scales through total imaging of the photon flux.
Today’s digital cameras capture photons in packets of 10-100 thousand and provide them for external display or recording at fraction of second intervals. In order to process photons individually rather than as packets we must develop a camera operating 10-100 thousand times faster. Each pixel must be capable of capturing single photon parameters without compromising the high resolution and sensitivity achieved by current technology. The "total photon" camera will be realised in nanoscale CMOS technology, based on recent breakthroughs in ultra-miniature single-photon detectors. We will combine these with novel approaches to pixel circuits, image processing and high-speed readout electronics to provide a fundamental research tool for the emerging area of computational microscopy. We will provide access to the full record of photon emission from live cells, and hence the clearest possible visualization of dynamic cellular processes in a single device capable of wide-field molecular spectroscopy and superresolution imaging.
This project is in collaboration with Robert Henderson (UoE and ERC Grant Holder) to develop the next generation of microscope cameras capable of high speed, single photon counting for use in TCSPC and super-resolution microscopy. At Heriot-Watt we are involved in developing a testbed for these cameras on our existing super-resolution microscopes with novel biological applications. Specific aims are:
- To iteratively develop new cameras with feedback from real world testing
- To apply new CMOS cameras to super-resolution imaging and TCSPC spectroscopy
- Examine molecular behaviour in regulated secretion
This project is funded by: