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Microscopy

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Temperature Jump Dynamics Microscope An apparatus and methods for characterizing the response of a particle to a parameter that characterizes an environment of the particle. A change is induced in the... Read More An apparatus and methods for characterizing the response of a particle to a parameter that characterizes an environment of the particle. A change is induced in the parameter characterizing the environment of the particle, where the change is rapid on a timescale characterizing kinetic response of the particle. The response of the particle is then imaged at a plurality of instants over the course of a period of time shorter than the timescale characterizing the kinetic response of the particle. The response may be detected by measuring a temperature jump or by measuring correlation and anticorrelation between probe parameters across pixels. More particularly, the particle may be a molecule, such as a biomolecule, and the environment, more particularly, may be a biological cell. The parameter characterizing the environment of the particle may be a temperature, and change may be induced in the temperature by heating a volume that includes the particle, either conductively or radiatively. The volume may be heated by means of a laser, such as an infrared laser, for example, or by microwave heating. This technology produces highly spatial and temporally resolved microscopic images of induced relaxation dynamics through the combination of microscopy with a temperature jump in materials and biosystems under observation. Compatible with a variety of microscopy techniques, the technology allows for fast and controlled temperature change. Initiation of dynamics can also be achieved in a variety of systems, including chemical, physical, and biological systems. This technology can be applied to the observation of real-time temperature dynamics inside living cells. Compared to current options in the market, the technology is cheaper to produce and better for observing the aforesaid conditions.
Near-Field Diffractive Microscope A near-field microscope using one or more diffractive elements placed in the near-field of an object to be imaged. A diffractive covers the entire object, thus signal may... Read More A near-field microscope using one or more diffractive elements placed in the near-field of an object to be imaged. A diffractive covers the entire object, thus signal may thereby be gathered from the entire object, and advantageously increase the signal-to-noise ratio of the resulting image, as well as greatly improve the acquisition speed. Near-field microscopy overcomes the limitation of conventional microscopy in that subwavelength and nanometer-scale features can be imaged and measured without contact. Conventional Near-field Scanning Optical Microscopes (NSOM) and Atomic Force Microscopes (AFM) used for collecting images of sub-wavelength features in nanostructures and biological samples are inherently slow and can damage the object they are imaging. Their resolution is limited by the aperture of the scanning tip; hence a low signal-to-noise ratio is achieved. This Near-field Diffractive Microscope (NDM) addresses these issues by collecting data from the entire scattering surface simultaneously without the need for a small aperture to achieve high resolution images. The Near-field Diffractive Microscope uses a Fresnel plate as a single diffractive element to provide all the spatial frequencies needed to collect exhaustive information from different regions of the sample. Screen Shot 2016-09-15 at 10.09.28 AM.png This optical device provides several benefits over the existing instruments, including increased speed of data collection and enhanced resolution. It has the potential to be of use in the imaging of samples from various fields - from life sciences to material science and in microlithography - where the ability to resolve atomic scale features with great speed and accuracy are crucial.
Interferometric Synthetic Aperture Microscopy (ISAM) Interferometric Synthetic Aperture Microscopy (ISAM) ISAM offers revolutionary technology advancement in OCT and other microscopy methods. With a single pass, the... Read More Interferometric Synthetic Aperture Microscopy (ISAM) ISAM offers revolutionary technology advancement in OCT and other microscopy methods. With a single pass, the algorithm is able to extend the range over which devices can scan an image by integrating data taken from non-focal point areas in addition to the focal region. Integration of the ISAM technology into catheters or arterial imaging devices would add significant value above the existing image rendering paradigms. Benefits Produces functional imagery from formerly unusable data Maintains quality resolution in high depth-of-field and 3-D applications Tolerates errors in defocus Employs digital processing to compensate for instrument and user error
Interferometric Synthetic Aperture Microscopy (ISAM) Using Partially Coherent Light Source Interferometric Synthetic Aperture Microscopy (ISAM) is a method of tomographic optical microscopy that brings the power of computed imaging and inverse scattering... Read More Interferometric Synthetic Aperture Microscopy (ISAM) is a method of tomographic optical microscopy that brings the power of computed imaging and inverse scattering together with interferometric broadband optical imaging. ISAM provides an extended three-dimensional resolution of objects, including regions away from the focus of the objective, and quantitative estimation of the inhomogeneities in refractive index or susceptibility of an object. Using a scanned beam in regular ISAM may have disadvantages, because, for very fast phenomena, the beam may not scan fast enough. While fully coherent ISAM provides the ability to take pictures in three-dimensional volumes in a fraction of a section, it is difficult to use in highly scattering samples. By decreasing the coherence one can reduce the multiple scattering component; however, the solution for the partially coherent ISAM case is different and therefore needs a separate derivation to find the mathematical relationship between object structure and data. This invention is full-field optical coherence tomographic microscopy with a source of varying spatial coherence. Description/Details The illumination system consists of a spatially incoherent source (e.g. filament of an incandescent light bulb), an iris to vary the apparent size of the source, and a collimation lens to collimate the source illumination. This system produces an adjustable partially coherent illumination at the source field plane. Data is acquired by tuning the wavelength of the source over a particular bandwidth while recording the intensity of interferograms on the focal plane array. A linear solution for the inverse scattering problem for partially coherent illumination is derived by computational models. Applications Tumor analysis Evaluation of surface topography Fluorescent microscopy Ideal for bench-top microscope-based systems Benefits Extended three-dimensional resolution Adjustable partially coherent illumination Fixes sample scatter and optics issues Less expensive as it does not require a separate reference telescope to relay the reference field
Near-Field Volume Scanning Optical Tomography The Near-field Volume Scanning Optical Tomography (NVSOT) improves upon the existing Near-field Scanning Optical Microscopy (NSOM) modalities by extending the data... Read More The Near-field Volume Scanning Optical Tomography (NVSOT) improves upon the existing Near-field Scanning Optical Microscopy (NSOM) modalities by extending the data acquisition to obtain the tomographic information of the sample without multi-directional measurements or multi-angle illuminations. Three-dimensional imaging is a much desired capability in the field of life sciences and nanotechnology; current techniques require multiple image acquisitions and complicated optical set-up. Measurement of the volume above the sample with a strongly scattering tip in the NVSOT based system induces higher order interactions which contains the tomographic information required to generate a three-dimensional image of the sample. Near-field Volume Scanning Optical Tomography (NVSOT) enables collection of tomographic data for the reconstruction of three dimensional images of sub-wavelength scale samples in the near-field of a strongly scattering tip. This technology eliminates the need for multi-directional measurements of the scattered field in the illumination mode or multi-angle illuminations in the collection mode. Scanning the three dimensional volume above the sample amounts to acquiring multiple NSOM images, data independence is ensured by the higher order interactions between the probe tip and the sample. Applications For optical microscopy and three-dimensional imaging of sub-wavelength scale samples in the fields of: Biological Sciences Material Sciences Nanotechnology Benefits Volume scan of the surface above the sample with a strongly scattering tip enables tomographic reconstruction of the sample. Eliminates the need for multi-directional measurements of the scattered field in the illumination mode. Eliminates the need for multi-angle illumination for measurements in the collection mode. The higher order interaction between the sample and the tip ensure data independence.
Spectroscopic Near-Field Scanning Optical Tomography The development of near-field scanning optical microscopy (NSOT) has been driven by the need for an imaging technique that retains the various contrast mechanisms... Read More The development of near-field scanning optical microscopy (NSOT) has been driven by the need for an imaging technique that retains the various contrast mechanisms afforded by optical microscopy methods while attaining spatial resolution beyond the classical optical diffraction limit. NSOT, as an extension of near-field scanning optical microscopy (NSOM), amounts to inverting the scattering data collected by the NSOM and reconstructing the sample, instead of taking the raw data as an image of the sample. This invention is a new method to simplify realization of NSOT and reduce mechanical and other noises. This invention also proposes an alternative NSOT modality to improve the experimental feasibility of NSOT. For ultra-high optical resolution, near-field scanning optical microscopy (NSOM) is currently the photonic instrument of choice. Near-field imaging occurs when a sub-micron optical probe is positioned a very short distance from the sample and light is transmitted through a small aperture at the tip of this probe. The near-field is defined as the region above a surface with dimensions less than a single wavelength of the light incident on the surface. Within the near-field region evanescent light is not diffraction limited and nanometer spatial resolution is possible. This phenomenon enables non-diffraction limited imaging and spectroscopy of a sample that is simply not possible with conventional optical imaging techniques. In addition, rather than using multiple observation angles or multiple probes, it is possible to collect data in a third dimension using the spectral degree of freedom. The idea of constructing an image in N spatial dimensions by collecting data in (N - 1) spatial dimensions and a spectral dimension has found application in techniques such as optical coherence tomography and synthetic aperture radar. Applications Any high magnification microscopy, with requirements short of a scanning electron microscope. Benefits This method clarifies the ambiguity between the sample and its NSOM image, and by inverting multiple NSOM images of a three-dimensional sample, a three-dimensional tomography of the sample may be obtained. Multiple images corresponding to different wavelengths can be collected from each probe scan and are therefore inherently co-registered.
Inverse Scattering for Broadband Scanning Near-Field Microscopy The development of near-field scanning optical microscopy (NSOT) has been driven by the need for an imaging technique that retains the various contrast mechanisms... Read More The development of near-field scanning optical microscopy (NSOT) has been driven by the need for an imaging technique that retains the various contrast mechanisms afforded by optical microscopy methods while attaining spatial resolution beyond the classical optical diffraction limit. NSOT, as an extension of near-field scanning optical microscopy (NSOM), amounts to inverting the scattering data collected by the NSOM and reconstructing the sample, instead of taking the raw data as an image of the sample. This invention is a new method to simplify realization of NSOT and reduce mechanical and other noises. This invention also proposes an alternative NSOT modality to improve the experimental feasibility of NSOT. For ultra-high optical resolution, near-field scanning optical microscopy (NSOM) is currently the photonic instrument of choice. Near-field imaging occurs when a sub-micron optical probe is positioned a very short distance from the sample and light is transmitted through a small aperture at the tip of this probe. The near-field is defined as the region above a surface with dimensions less than a single wavelength of the light incident on the surface. Within the near-field region evanescent light is not diffraction limited and nanometer spatial resolution is possible. This phenomenon enables non-diffraction limited imaging and spectroscopy of a sample that is simply not possible with conventional optical imaging techniques. In addition, rather than using multiple observation angles or multiple probes, it is possible to collect data in a third dimension using the spectral degree of freedom. The idea of constructing an image in N spatial dimensions by collecting data in (N - 1) spatial dimensions and a spectral dimension has found application in techniques such as optical coherence tomography and synthetic aperture radar. Applications Any high magnification microscopy, with requirements short of a scanning electron microscope. Benefits This method clarifies the ambiguity between the sample and its NSOM image, and by inverting multiple NSOM images of a three-dimensional sample, a three-dimensional tomography of the sample may be obtained. Multiple images corresponding to different wavelengths can be collected from each probe scan and are therefore inherently co-registered.
Jones Phase Microscopy of Transparent and Anisotropic Samples The phase contrast microscope is a vital instrument in biological and medical research; it facilitates the observation of living cells by using spatial light modulation to... Read More The phase contrast microscope is a vital instrument in biological and medical research; it facilitates the observation of living cells by using spatial light modulation to enhance the intrinsic contrast of transparent and colorless components in a cell. It can reveal cell structure without the need of contrast agents. However, the information obtained is only qualitative. Jones Phase Microscopy (JPM) and White Light Quantitative Phase Microscopy (PC++) of transparent and anisotropic samples are novel interferometric techniques that are quantitative and polarization sensitive. They are capable of quantifying the optical phase delays associated with live cell samples while providing information about the morphology and dynamics. Quantifying these optical path length shifts allows for nanometer scale measurements with broad applications in nanotechnology and life sciences, e.g. from inspecting semiconductor wafers to studying processes in live cells. Description/Details Jones Phase Microscopy (JPM) technique is capable of extracting the spatially-resolved Jones matrix associated with transparent and anisotropic samples. It can provide the quantitative phase image of the cells as well as the intrinsic structure details and dynamics. JPM setup consists of a modified Hilbert Phase microscope; the quantitative phase image is correlated to the sample using a 2D spatial Hilbert transform. The full Jones matrix in each point within the field associated with the transparent sample is extracted and the embedded quantitative information of phase delay is used to reconstruct its image. The White Light Quantitative Phase Microscope (PC++) interfaces with a commercial phase contrast microscope and transforms it into a quantitative instrument by performing two additional measurements (hence the name PC++). In a conventional phase microscope the additional phase delay is introduced by the phase objective, the PC image is delivered at the image plane and recorded by a CCD. However, in PC++, the optical field at the image plane is further modulated before detection which is equivalent to spatial filtering with three different phase masks and reconstruction of image by addition of fields containing information about the unscattered light (forming the uniform background) and the fine structural details (the contrast). Applications Optical microscopy and imaging of: live cells and thin tissue slices; microorganisms; lithographic patterns and nanoparticles Study of cell dynamics and morphology Benefits These techniques provide improved contrast in unstained biological specimens and can be utilized to examine dynamic events in living cells. Quantitative Phase delay information Polarization sensitive imaging: while Jones Phase Microscope is a modified Hilbert Phase microscope, the PC++ is an add-on to a commercial phase contrast microscope.
White Light Quantitative Phase Microscopy PC++ The phase contrast microscope is a vital instrument in biological and medical research; it facilitates the observation of living cells by using spatial light... Read More The phase contrast microscope is a vital instrument in biological and medical research; it facilitates the observation of living cells by using spatial light modulation to enhance the intrinsic contrast of transparent and colorless components in a cell. It can reveal cell structure without the need of contrast agents. However, the information obtained is only qualitative. Jones Phase Microscopy (JPM) and White Light Quantitative Phase Microscopy (PC++) of transparent and anisotropic samples are novel interferometric techniques that are quantitative and polarization sensitive. They are capable of quantifying the optical phase delays associated with live cell samples while providing information about the morphology and dynamics. Quantifying these optical path length shifts allows for nanometer scale measurements with broad applications in nanotechnology and life sciences, e.g. from inspecting semiconductor wafers to studying processes in live cells. Description/Details Jones Phase Microscopy (JPM) technique is capable of extracting the spatially-resolved Jones matrix associated with transparent and anisotropic samples. It can provide the quantitative phase image of the cells as well as the intrinsic structure details and dynamics. JPM setup consists of a modified Hilbert Phase microscope; the quantitative phase image is correlated to the sample using a 2D spatial Hilbert transform. The full Jones matrix in each point within the field associated with the transparent sample is extracted and the embedded quantitative information of phase delay is used to reconstruct its image. The White Light Quantitative Phase Microscope (PC++) interfaces with a commercial phase contrast microscope and transforms it into a quantitative instrument by performing two additional measurements (hence the name PC++). In a conventional phase microscope the additional phase delay is introduced by the phase objective, the PC image is delivered at the image plane and recorded by a CCD. However, in PC++, the optical field at the image plane is further modulated before detection which is equivalent to spatial filtering with three different phase masks and reconstruction of image by addition of fields containing information about the unscattered light (forming the uniform background) and the fine structural details (the contrast). Applications Optical microscopy and imaging of live cells and thin tissue slices, microorganisms, lithographic patterns, and nanoparticles Study of cell dynamics and morphology Benefits These techniques provide improved contrast in unstained biological specimens and can be utilized to examine dynamic events in living cells. Quantitative Phase delay information Polarization sensitive imaging; while Jones Phase Microscope is a modified Hilbert Phase microscope, the PC++ is an add-on to a commercial phase contrast microscope.
Coherent Fiber Continuum Source Centered at 1040nm by In Situ Transform-Limited Pulse Compression A method using standard, inexpensive components and software to generate ultra-short laser pulses of a quality currently available only from complex, costly... Read More A method using standard, inexpensive components and software to generate ultra-short laser pulses of a quality currently available only from complex, costly systems, such as the Ti:Sapphire laser. Ultra-short laser pulses, shorter than 10 - 15 femtoseconds, are used in many applications including: multiphoton microscopy, coherent anti-Stokes Raman spectroscopy, and femtochemistry. At this time, such precision ultra-short pulse lasers are largely cost prohibitive in many applications, relatively difficult and expensive to maintain, and tend to be unreliable. This laser system was designed to provide a cost effective alternative to current femtosecond lasers. Applications: Research: multiphoton imaging, coherent anti-Stokes Raman spectroscopy, femtochemistry, and selective gene transfection Medical: skin imaging and pathology using multiphoton imaging Benefits: Ultra-short pulses: this technology allows tunable pulse compression capable of producing pulses ranging from 220 to 8.7 femtoseconds. Due to the simplicity of this system, once configured, the pulses are fully reproducible, need little maintenance and have excellent reliability. Size and portability: while Ti:Sapphire lasers require a significant amount of space, this system requires much less (it is roughly the size of a bread box) thereby allowing dramatically improved portability for easier translation to clinical applications, or inter-laboratory sharing and collaboration. Cost: at a fraction of the cost of a Ti:Sapphire laser, this invention provides a cost-effective alternative to all other commercially available femtosecond lasers. Reliability: the simple elegance of this laser system grants it excellent pulse reproducibility and reliability in contrast to currently available femtosecond lasers which, due to complexity and other factors, suffer from high maintenance costs and unreliability. Additionally, maintenance of this system is comparatively inexpensive because of its off-the-shelf standard components.

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