This Small Business Innovation Research Phase I project will establish the feasibility of transforming a wide-field optical microscope into a real-time imaging/metrology system. The system will have a spatial resolution better than 10 nanometers, when used as a wide-field optical microscope, and better than 1 Angstrom when used as a position tracker for nanoscale particles. Recent progress reaching effective resolutions below the Rayleigh diffraction limit of ~200 nm has spurred research in the fields of medical imaging and micro metrology. However, these optical microscopes and interferometers rely on a temporal image formed on an image sensor for the intensity and phase map calculation, which makes it difficult to isolate the measurement from vibration and other noise. In order to mitigate this issue, we will develop a system which integrates (1) an active optoelectronic mixing method to provide fast, synchronous phase-amplitude detection within a single frame acquisition time with high signal-to-noise and dynamic range, (2) a picometer-resolution motion scanner for precise active positioning of the pixel and/or structured illumination pattern with real-time super-resolution image reconstruction and (3) a real-time signal processing engine to solve the complicated inverse filter problem, to allow fast processing and better image resolution.
The broader impact/commercial potential of this project is to provide an economical add-on solution to optical microscopes to enhance observation and metrology performance to a level which is comparable to much more expensive electron microscopy or scanning probe systems. The resulting add-on system will allow many researchers and industrial users to significantly enhance their existing optical microscopes' performance at a fraction of the cost of conventional high-resolution imaging systems. The proposed system is expected to increase imaging productivity for manufacturing process evaluation and quality inspection in the fields of biomedical science, semiconductor devices, data storage and optical components. The new imaging capability, integrated with a quantitative phase measurement capability, is not only useful for life science (for example, for understanding system behavior at the molecular level in living cells), but also vital for inspecting and measuring surface parameters and nanoscale particle behavior for semiconductor manufacturers, makers of high precision optical components, and others involved in the fabrication and inspection of nanoscale materials and systems.
This Small Business Innovation Research (SBIR) project aims to develop a breakthrough technology which improves the performance of optical microscopes by approximately a factor of 10. There is a limit to microscope imaging resolution, called the Rayleigh diffraction limit, achievable by conventional optical microscopes due to the light diffraction phenomenon. For conventional optical microscopes this limit is about 200nm. Electron microscopes, on the other hand cannot observe live biological samples due to the special preparation needed and the requirement for observation in vacuum condition. Over the past 10-15 years, new technologies aimed at exceeding the Rayleigh diffraction limit have been developed. These technologies are generally called Super-Resolution Microscopy (SRM) and usually involve trade-offs between imaging resolution, signal-to-noise-ratio (SNR) and image acquisition speed. High acquisition speed is necessary to observe fast biological phenomena which can be on the order of a millisecond, while the time to acquire a single image using other SRM technologies can be minutes or even hours. NanoWave’s method combines its patented synchronous detection method, and classical structured illumination using high-density fringe projection to create a high SNR and high spatial resolution microscope and particle tracking system without the trade-off of image acquisition speed. During Phase I of this SBIR project, in addition to numerical simulation, a custom prototype microscope was built to verify some of the theories that were proposed. A study on the use of a GPU (Graphic Processing Unit) to speed up the computation of the signal processing was also studied. Through the combination of simulation and actual data measurements using the synchronous detection method, NanoWave proved the feasibility of a 20nm spatial resolution imaging microscope and showed that a 50 times noise level improvement and 3 times contrast improvement, when compared to a conventional optical microscope, could be achieved. NanoWave also showed that a 0.1nm particle tracking can be achieved and total computation time can be reduced up to 10x with the use of GPU hardware during Phase I of this research. One of the broader impacts of this research project is in the field of biomedical research. One of the goals of a large class of biomedical research is to observe the behavior of cells, proteins, molecules, or viruses in order to develop rules that describe or predict their behavior. Having this understanding allows investigators to gain insight into the mechanisms for the spread of disease, for drug delivery, and for a host of other processes. Further, having such rules facilitates contrasting normal behavior with behavior influenced by new drugs, by disease, etc. NanoWave’s proposed method will provide a wide field optical microscope with sub-diffraction resolution where traditionally only SEM (Scanning Electron Beam) equipment can achieve reasonable resolution and imaging frame rates. NanoWave’s planned technology will allow biomedical researchers the capability of studying molecular phenomena in their natural condition, which has been previously impossible. When observing tagged molecules or cell, the system provides sub-nanometer repeatability in determining the center position of these particles over long motion range. Multiple particle positions and sizes can be monitored in real-time. NanoWaves’ new class of imaging capability is not only useful for life science but also for inspecting and measuring substrates, wafers, and nanosize particle behavior in semiconductor, high precision optics and other nano technology related manufacturing.
