2036 results about "Microscopy" patented technology

The present invention relates to systems and methods for quantitative three-dimensional mapping of refractive index in living or non-living cells, tissues, or organisms using a phase-shifting laser interferometric microscope with variable illumination angle. A preferred embodiment provides tomographic imaging of cells and multicellular organisms, and time-dependent changes in cell structure and the quantitative characterization of specimen-induced aberrations in high-resolution microscopy with multiple applications in tissue light scattering.

Dendritic polymers with enhanced amplification and interior functionality are disclosed. These dendritic polymers are made by use of fast, reactive ring-opening chemistry (or other fast reactions) combined with the use of branch cell reagents in a controlled way to rapidly and precisely build dendritic structures, generation by generation, with cleaner chemistry, often single products, lower excesses of reagents, lower levels of dilution, higher capacity method, more easily scaled to commercial dimensions, new ranges of materials, and lower cost. The dendritic compositions prepared have novel internal functionality, greater stability (e.g., thermal stability and less or no reverse Michael's reaction), and reach encapsulation surface densities at lower generations. Unexpectedly, these reactions of polyfunctional branch cell reagents with polyfunctional cores do not create cross-linked materials. Such dendritic polymers are useful as demulsifiers for oil/water emulsions, wet strength agents in the manufacture of paper, proton scavengers, polymers, nanoscale monomers, calibration standards for electron microscopy, making size selective membranes, and agents for modifying viscosity in aqueous formulations such as paint. When these dendritic polymers have a carried material associated with their surface and/or interior, then these dendritic polymers have additional properties for carrying materials due to the unique characteristics of the dendritic polymer, such as for drug delivery, transfection, and diagnostics.

The methods and reagents described in this invention are used to analyze circulating tumor cells, clusters, fragments, and debris. Analysis is performed with a number of platforms, including flow cytometry and the CellSpotter® fluorescent microscopy imaging system. Analyzing damaged cells has shown to be important. However, there are two sources of damage: in vivo and in vitro. Damage in vivo occurs by apoptosis, necrosis, or immune response. Damage in vitro occurs during sample acquisition, handling, transport, processing, or analysis. It is therefore desirable to confine, reduce, eliminate, or at least qualify in vitro damage to prevent it from interfering in analysis. Described herein are methods to diagnose, monitor, and screen disease based on circulating rare cells, including malignancy as determined by CTC, clusters, fragments, and debris. Also provided are kits for assaying biological specimens using these methods.

The present invention relates to confocal self-interference microscopy. The confocal self-interference microscopy further includes a first polarizer for polarizing reflected or fluorescent light from a specimen, a first birefringence wave plate for separating the light from the first polarizer into two beams along a polarizing direction, a second polarizer for polarizing the two beams from the first birefringence wave plate, a second birefringence wave plate for separating the two beams from the second polarizer into four beams along the polarizing direction, and a third polarizer for polarizing the four beams from the second birefringence wave plate, in the existing confocal microscopy. Optic-axes of the first and second birefringence wave plates exist on the same plane, optic-axes of the first and second birefringence wave plates are inclined from an optical axis of the entire optical system at a predetermined angle, and self-interference spatial periods of the first and second birefringence wave plates are different from each other.

In a spectroscopic microscope, a video image of a specimen is analyzed to identify regions having different appearances, and thus presumptively different properties. The sizes and locations of the identified regions are then used to position the specimen to align each region with an aperture, and to set the aperture to a size appropriate for collecting a spectrum from the region in question. The spectra can then be analyzed to identify the substances present within each region of the specimen. Information on the identified substances can then be presented to the user along with the image of the specimen.

A method and apparatus for three dimensional optical microscopy is disclosed which employs dual opposing objective lenses about a sample and extended incoherent illumination to provide enhanced depth or Z.Iadd.-.Iaddend.direction resolution. In a first embodiment, observed light from both objective lenses are brought into coincidence on an image detector and caused to interfere thereon by optical path length adjustment. In a second embodiment, illuminating light from an extended incoherent light source is detected to the sample through both objective lenses and caused to interfere with a section of the sample by adjusting optical path lengths. Observed light from one objective lens is then recorded. In a third embodiment, which combines the first two embodiments, illuminating light from an extended incoherent light source is directed to the sample through both objective lenses and caused to interfere within a section of the sample by adjusting optical path lengths. The observed light from both lenses is caused to interfere on the image detector by the same optical path length adjustment. .Iadd.In a fourth embodiment of the invention, further spatial structure is introduced into the illumination light. Computational processing is used to enhance lateral or XY resolution as well as depth or Z resolution..Iaddend.

A method for detecting single copies of a gene in-situ using brightfield microscopy is used in detection of nucleic acid sequences. Probes are directly or indirectly labeled with alkaline phosphatase with NBT/BCIP used as the chromogen.

The invention comprises a robotic microscope system and methods that allow high through-put analysis biological materials, particularly living cells, and allows precise return to and re-imaging of the same field (e.g., the same cell) that has been imaged earlier. This capability enables experiments and testing hypotheses that deal with causality over time intervals which are not possible with conventional microscopy methods.

An apparatus and method for performing nucleic acid (DNA and/or RNA) sequencing on a single molecule. The genetic sequence information is obtained by probing through a DNA or RNA molecule base by base at nanometer scale as though looking through a strip of movie film. This DNA sequencing nanotechnology has the theoretical capability of performing DNA sequencing at a maximal rate of about 1,000,000 bases per second. This enhanced performance is made possible by a series of innovations including: novel applications of a fine-tuned nanometer gap for passage of a single DNA or RNA molecule; thin layer microfluidics for sample loading and delivery; and programmable electric fields for precise control of DNA or RNA movement. Detection methods include nanoelectrode-gated tunneling current measurements, dielectric molecular characterization, and atomic force microscopy/electrostatic force microscopy (AFM/EFM) probing for nanoscale reading of the nucleic acid sequences.

Systems and methods for performing inspection and metrology operations on metallization processes such as on back-end-of-line (BEOL) metallization thickness and step coverage are disclosed. Specific examples include measurements of thickness and uniformity of barrier layers, including tantalum for example, and seed layers, including copper for example, in Damascene, including dual-Damascene, trenches during the interconnect fabrication steps of integrated circuit production. The invention also relates to the detection and measurement of void formation during and after copper electroplating. The invention utilizes x-ray fluorescence to measure the absolute thicknesses and the thickness uniformity of the barrier layers in the trenches, the copper seed layers for electroplating, and the final copper interconnects.

The invention enables in situ genomic and transcriptomic assessment of nucleic acids to be conducted in biological specimens that have been physically expanded. The invention leverages the techniques for expansion microscopy (ExM) to provide new methods for in situ genomic and transcriptomic assessment of nucleic in a new process referred to herein as “expansion fluorescent in situ hybridization” (ExFISH).

One embodiment relates to a method of inspecting a substrate using electrons. Mirror-mode electron-beam imaging is performed on a region of the substrate at multiple voltage differences between an electron source and a substrate, and image data is stored corresponding to the multiple voltage differences. A calculation is made of a measure of variation of an imaged aspect of a feature in the region with respect to the voltage difference between the electron source and the substrate. Other embodiments and features are also disclosed.

This invention relates to imaging, such as by expansion microscopy, labelling, and analyzing biological samples, such as cells and tissues, as well as reagents and kits for doing so.

The invention relates to scanning pulsed laser systems for optical imaging. Coherent dual scanning laser systems (CDSL) are disclosed and some applications thereof. Various alternatives for implementation are illustrated. In at least one embodiment a coherent dual scanning laser system (CDSL) includes two passively modelocked fiber oscillators. In some embodiments an effective CDSL is constructed with only one laser. At least one embodiment includes a coherent scanning laser system (CSL) for generating pulse pairs with a time varying time delay. A CDSL, effective CDSL, or CSL may be arranged in an imaging system for one or more of optical imaging, microscopy, micro-spectroscopy and/or THz imaging.

The invention provides a system and method for automatic real-time monitoring for the presence of a pathogen in water using coherent anti-stokes Raman scattering (CARS) microscopy. Water sample trapped in a trapping medium is provided to a CARS imager. CARS images are provided to a processor for automatic analyzing for the presence of image artifacts having pre-determined features characteristic to the pathogen. If a match is found, a CARS spectrum is taken and compared to a stored library of reference pathogen-specific spectra for pathogen identification. The system enables automatic pathogen detection in flowing water in real time.

The invention relates to scanning pulsed laser systems for optical imaging. Coherent dual scanning laser systems (CDSL) are disclosed and some applications thereof. Various alternatives for implementation are illustrated, including highly integrated configurations. In at least one embodiment a coherent dual scanning laser system (CDSL) includes two passively modelocked fiber oscillators. The oscillators are configured to operate at slightly different repetition rates, such that a difference δf_r in repetition rates is small compared to the values f_r1 and f_r2 of the repetition rates of the oscillators. The CDSL system also includes a non-linear frequency conversion section optically connected to each oscillator. The section includes a non-linear optical element generating a frequency converted spectral output having a spectral bandwidth and a frequency comb comprising harmonics of the oscillator repetition rates. A CDSL may be arranged in an imaging system for one or more of optical imaging, microscopy, micro-spectroscopy and/or THz imaging.