Dmetrix, Inc.

Amazon Technologies, Inc.

Arizona Board of Regents on Behalf of the University of Arizona

Azbil Biovigilant, Inc.

Dhetrix, Inc.

Azbil Corporation

Chen Liang

Artur Olszak

Pixuan Zhou

Michael R Descour

Ronald S Weinstein

Peter H Bartels

Roland V Shack

Todd Richard Christenson

Angeles Marcia Almanza-Workman

John Y Babico

Pierre-Alexandre Blanche

Xuemeng Zhang

James Goodall

Arkady Bablumyan

Techniques for an optical lens set and optical combiner are described herein. In an example, an apparatus has a first side and a second side. The apparatus includes an optical combiner and a first optical lens disposed at the first side. The image combiner is configured to output light emitted by a light projector as a virtual image projection within a field of view. At least a first portion of the first optical lens is within the field of view and is characterized by a first optical power that provides a first optical correction. The first optical power compensates for a second optical power of a second optical lens optionally disposable at the second side.

Optical lens set and image combiner

The present invention features new waveguide layouts for input, redirection (expansion), and output holograms that minimize cross talk between colors and allow all three colors to reside in a single waveguide. The use of multiple incoupling holograms that diffract different colors of light in different directions, or along different paths, through a waveguide substrate advantageously provides for a reduction of cross-talk between the colors of a holographic image. In a square-shaped design, red, green, and blue input and output holograms approximately overlay on top of each other. The green redirection hologram is laterally separated from the red and blue redirection holograms. Using this square-shape design, the light beams for the three colors are separated into two paths propagating from input to output holograms.

Waveguide geometry for improved display performance

A method for operating a scanning microscope system. The optimal number of required through-focus scans, that is required to predict the position of a focal plane of the objective with respect to the object to produce the image with minimized blur, is not pre-determined but rather defined iteratively in real-time, contemporaneously with conducting the sample scanning operation itself.

Prediction of a focal plane with progressive through-focus scans

System and method for correcting a topography of an object being imaged by a multi-array microscope system. The object is forced to conform to a surface of the substrate supporting the object with a suction force and the topography of the chosen object surface is determined. The supporting substrate is bent with the use of force applied to the substrate with at least one actuator such as to reduce the deviations of the determined topography of the object's surface from a pre-determined reference surface by transferring the changes in the curvature of the supporting substrate to the object. In particular, the chosen surface of the object can be substantially flattened for ease of simultaneous imaging of this surface with multiple objectives of the multi-array microscope.

Manipulation of topography of large-format glass slides

A method for object preparation for imaging with an array microscope system without scanning. Artifact-free image is formed based on scanning-free imaging of an object array formed from spatially-separated portions of the initially spatially-continuous object that are arranged, in the object plane of the array microscope, in a pattern associated with an array of individual objectives of the array microscope. The size of an individual portion of the object does not exceed the size of a FOV of the individual objective defined in the object plane.

Matching object geometry with array microscope geometry

Method and system of interferometrically measuring, in reflection, a non-spherical surface with two diffracted beams (of different diffraction orders) formed by a diffractive element positioned transversely to the axis of a common-path interferometer. The first diffracted beam substantially maintains the wavefront of a beam incident onto the diffractive element, while the second diffracted beam has a wavefront profile corresponding to the profile of the measured surface. The first diffracted beam may be reflected by the surface in a cat's eye configuration, while the second diffracted beam is reflected by the surface in a confocal configuration. The surface being measured can be modified to substantially balance radiant powers of the first and second diffracted beams upon reflection off the surface.

Interferometric apparatus with computer-generated hologram for measuring non-spherical surfaces

Two-dimensional scanning array microscope system, which has fields of view of individual objectives overlapping at the object, produces a composite image of the object that is devoid of optical distortions caused by such overlapping. Method for processing imaging data with the system includes precise identification of detector pixels corresponding to different portions of multiple image swaths projected on the detector by the system during the scan of the object, and, based on such identification, allocating or assigning of detector pixels that receive light from the object through more than one objective to only one of objectives, thereby correcting imaging data received in real time to remove a portion of data corresponding to image overlaps.

Correction of a field-of-view overlay in a multi-axis projection imaging system

A particle detection and classification system is disclosed. The system determines the size of measured particles by measuring light scattered by the particles. The system simultaneously determines whether measured particles are biological or non-biological by measuring fluorescent light from the particles. The system uses a parabolic reflector, and optionally, a spherical reflector to collect fluorescence light.

Compact detector for simultaneous particle size and fluorescence detection

An imaging apparatus consists of multiple miniaturized microscopes arranged into an array capable of simultaneously imaging respective portions of an object. A continuous linear translation approach is followed to scan the object and generate multiple image swaths of the object. In order to improve the quality of the composite image produced by concatenation of the image swaths, the performance of each microscope is normalized to the same base reference for each relevant optical-system property. Correction factors are developed through calibration to equalize the spectral response measured at each detector, to similarly balance the gains and offsets of the detector/light-source combinations associated with the various objectives, to correct for geometric misalignments between microscopes, and to correct optical and chromatic aberrations in each objective.

Large-area imaging by concatenation with array microscope

An array microscope scans a slide in rapid sequence at different wavelengths to record multiple spectral images of the sample. Full spatial resolution of the image sensor is realized at each color because pixels are not shared between spectral bands. The object and detector are placed at conjugate distances selected to produce substantially equal magnification with minimum chromatic aberration at all wavelengths to ensure registration of all images. Spectral analysis is carried out by combining the images captured at each wavelength. The greater-than-RGB spectral resolution provided by the combination of images enables the isolation and display of the effects produced by the contemporaneous use of more than two stains on a tissue for improved pathological analysis.

Multi-spectral whole-slide scanner

A liquid lens includes a segmented electrode that allows the simultaneous application of different potentials across the lens's meniscus to obtain a predetermined aberration correction condition and to adjust focal length as necessary to conform to the topography of the object being scanned. The lens also includes a gas plenum interfacing with one of the liquids of the lens to allow for volume changes in the lens cell due to temperature variations. This combination of features produces a liquid-lens cell capable of maintaining substantially constant transverse magnification and diffraction-limited image quality over a useful range of focal length. As such, the lens is particularly suitable for incorporation in an array of micro-objectives used in a scanning microscope.

Liquid-lens variable-control optics in array microscope

A single-axis illumination system for a multiple-axis imaging system, particularly an array microscope. A single-axis illumination system is used to trans-illuminate an object viewed with an array of imaging elements having multiple respective axes. The numerical apertures of the imaging elements are preferably matched to the numerical aperture of the illumination system. For Kohler illumination, the light source is placed effectively at the front focal plane of the illumination system. For critical illumination, the light source is effectively imaged onto the object plane of the imaging system. For dark field illumination, an annular light source is effectively provided. For phase contrast microscopy, an annular phase mask is placed effectively at the back focal plane of the objective lens of the imaging system and a corresponding annular amplitude mask is provided effectively at the light source. For Hoffman modulation contrast microscopy, an amplitude mask is placed effectively at the back focal plane of the objective lens of the imaging system and a slit is provided at a source of light of the illumination system. Structured illumination and interferometry, and a secondary source, may also be used with trans-illumination methods and apparatus according to the present invention.

Single axis illumination for multi-axis imaging system

A multiple-axis imaging system having optical elements whose optimal image positions can be individually adjusted, comprising a plurality of optical array elements having respective optical axes and being individually disposed with respect to one another to image respective sections of an object; and a plurality of image position shifting devices corresponding to respective optical elements for separately establishing the image positions for a plurality of the optical array elements. The multi-axis imaging system preferably comprises a miniaturized microscope array. The shifting devices may comprise wavelength filters or optical-path-length-altering elements, such as a plane parallel plates. The devices may also comprise a pair of wedges that adjustably overlap one another, the wedges having apexes that point in opposite directions and respective corresponding planar surfaces that are parallel to one another. A method for separately adjusting the image positions of a plurality of optical elements in a multi-axis imaging system is also provided, particularly in an array microscope.

Independent focus compensation for a multi-axis imaging system

An epi-illumination system for an array microscope. For Kohler illumination, illumination light sources are placed, actually or virtually, at the pupils of respective individual microscope elements of an array microscope. In one Kohler illumination embodiment, the light source is a point source comprising the tip of an optical fiber placed on the optical axis at the pupil of its corresponding microscope element. In another Kohler illumination embodiment, the illumination light is provided by a reflective boundary placed on the optical axis of a corresponding microscope element. For critical illumination the light sources are placed at locations conjugate with their respective object planes so as to image the light sources thereon. For dark-field illumination, the support material around a microscope element lens, which is used to support an array of lenses, is fashioned to form an illumination optical element so that light from an off-axis source is directed by the illumination element toward the object plane at an angle such that light will not be reflected into the field of view of the imaging system, but scattered or fluorescence light will be within that field of view. The illumination optical element may be refractive element, a Fresnel element, a reflective element, a diffractive element, or some combination of one or more of these elements. An array of pinhole apertures may be provided to operate the array microscope in a confocal mode. All of the embodiments may be used for epi-fluorescence microscopy.

Growing community of inventors

Tucson, AZ, United States of America

Chen Liang