Optical microscopy is the most commonly used imaging technique in life and material sciences; however, the spatial resolution of any standard microscope is fundamentally limited by the diffraction of light waves which for visible light restricts spatial resolution to ~250 nm. Surpassing the diffraction-limit significantly impacts several disciplines, such as medical and material sciences, microfluidics, and nanophotonics, and therefore has been the subject of considerable research effort. Several imaging techniques based on near-field scanning probes and various fluorescent-based schemes have been developed in the past to overcome the diffraction-limit. These techniques, however, are associated with a complex design and high economic cost, and require dedicated equipment and scanning across the specimen that increases the image acquisition time; furthermore, near-field scanning leads to significant loss of optical throughput and fluorescent-based methods are applicable only to specimens that are decorated with fluorophores. We have focused on developing a simple generic super-resolution imaging method. Specifically, we recently demonstrated feasibility of imaging biological and photonic structures, with resolution improvement by a factor of 2-3, by using novel super-resolution microscope slides (SRMS) composed of a monolayer array of microspheres, with high index of refraction, fixed in a transparent elastomer layer. The slides are simply placed over the specimen under investigation as a coverslip to increase the image spatial resolution of a standard microscope. The objective of this proposal by SphereVis is toward the development of low-cost technologies for global health by developing the technology of mass-fabrication of optimized novel super-resolution microscope slides as a commercial product. The proposed SRMS provides medical science researchers with a new tool for cancer biology research and has a broad range of applications, allowing super-resolution imaging of biological, metallic, and semiconductor structures. We will design and fabricate SRMS and characterize their imaging properties, i.e. resolution gain, magnification, and field-of-view, for different schemes of SRMS to optimize the design parameters for application in ?-H2AX assay of proton-irradiated V79 and U87 cancer cell lines.
Public Health Relevance Statement: Public Health Relevance: Microscopic imaging has traditionally been constrained by the diffraction limit, which for visible light restricts spatial resolution to ~250 nm. Surpassing thislimit would significantly benefit several disciplines, such as medical and material sciences. Our company, SphereVis LLC, has developed a simple generic super-resolution method for biological and photonic structures that provides two- to three-fold-enhancement in spatial resolution.
Project Terms: Air; anticancer research; Area; Award; Barium; base; Biological; Biological Assay; Biological Sciences; Cancer Biology; Cancer cell line; Carbon ion; Cell Line; Cell Survival; Cells; Characteristics; Chemistry; Complex; cost; design; Development; diffraction of light; Discipline; economic cost; Elastomers; Equipment; field theory; Fluorescence Microscopy; fluorophore; Generic Drugs; Glass; global health; Goals; Image; image processing; imaging modality; Imaging Techniques; Immersion Investigative Technique; indexing; Individual; Investigation; Kinetics; Laws; lens; Light Microscope; materials science; Measures; Medical; Methods; Microfluidics; Microscope; microscopic imaging; Microscopy; Microspheres; Modality; molecular imaging; monolayer; nanoscale; Nobel Prize; novel; Optics; particle; Pattern; photonics; Photons; Positioning Attribute; Probability; Property; Protons; prototype; public health relevance; Radiation; Radiation Induced DNA Damage; Radiation therapy; Refractive Indices; repaired; Reporting; Research; Research Personnel; Resolution; Scanning; Scheme; Science; Semiconductors; Slide; Specimen; Specimen Handling; Spectrum Analysis; Structure; Surface; System; Techniques; Technology; Thick; Time; tool; Training; Translating; Visible Radiation
