Ge Healthcare Bio-sciences Corp.

Applied Precision, Inc.

General Electric Company

Leica Microsystems Cms Gmbh

Ge Healthcare Bio-sciences Ab

Cytiva Sweden Ab

Global Life Sciences Solutions USA LLC

Ge Healthcare Biocience Bio-process Corp

Jeremy R Cooper

Paul Carlyle Goodwin

Steven A Reese

Justin Kyle Curts

Ronald C Seubert

Kyle Justin Curts

William Michael Dougherty

James T Newberry

Stephen G Goodson

Kathryn Buckanan

William M Dougherty

Jeffrey D Bert

Steven Allan Reese

Jeffrey David Bert

Disclosed is a cell culture microscopy slide comprising an optically transparent generally flat supporting surface () including upper and lower opposed substrate surfaces (). A peripheral frame () surrounds the substrate (), the frame () having a lower frame surface () and an upper frame surface (). The lower frame surface () and the lower substrate surface () are generally flush. The upper frame surface () lies above the upper substrate surface (), to form a well (), and the upper and lower frame surfaces () are continuously flat and generally parallel. The substrate is preferably glass having a thickness of 1.7 mm.

Cell culture microscopy slides

Disclosed is an LED arrangement for a microscopy instrument (FIG.) comprising a light emitting area (), and a part-spherical solid and light transmissive cap (), in light communication with the light emitting area, the cap having a hemispherical surface () including a portion () at which light from the light emitting area is reflected and a portion () at which light from the emitter can exit the cap, in order to provide a usable light cone L which includes light recycled from the more divergent emitted light, and is thereby more intense.

LED illumination in microscopy

Disclosed is an optical arrangement providing selective plane illumination, including an inverted illumination objective mounted below a sample support in use providing a line or plane of light at the sample support, and at least one image collection objective mounted above the support, said inverted illumination objective having an illumination objective optic axis, and said image collection objective having an image collection objective optical axis, wherein illumination light is arranged to propagate toward the illumination objective lateral offset to the illumination objective optical axis such that the illumination light leaving the illumination objective propagates toward the sample support at an oblique angle relative to the illumination objective optical axis, and wherein the image objective optical axis has an angle &#x3b1; which is obtuse to the illumination objective optical axis and generally perpendicular to light propagating at the sample support.

Selective plane illumination microscopy instruments

Embodiments of the present invention are directed to autofocus subsystems within optical instruments that continuously monitor the focus of the optical instruments and adjust distances within the optical instrument along the optical axis in order to maintain a precise and stable optical-instrument focus at a particular point or surface on, within, or near a sample. Certain embodiments of the present invention operate asynchronously with respect to operation of other components and subsystems of the optical instrument in which they are embedded. In one embodiment the autofocus detector comprises a beam splitter arranged to split the autofocus light beam into a plurality (n) of down-stream light beams and a photodetector arrangement for registering the intensity of each one of the down-stream light beams.

System and method for continuous, asynchronous autofocus of optical instruments

Variable orientation illumination-pattern rotators ('IPRs') that can be incorporated into structured illumination microscopy instruments to rapidly rotate an interference pattern are disclosed. An IPR includes a rotation selector and at least one mirror cluster. The rotation selector directs beams of light into each one of the mirror clusters for a brief period of time. Each mirror cluster imparts a particular predetermined angle of rotation on the beams. As a result, the beams output from the IPR are rotated through each of the rotation angles imparted by each of the mirror clusters. The rotation selector enables the IPR to rotate the beams through each predetermined rotation angle on the order of 5 milliseconds or faster.

Variable orientation illumination-pattern rotator

Microscopy instruments with detectors located on one side of the instruments are disclosed. The microscopy instruments include a splitting system and an array of detectors disposed on one side of the instrument. A beam composed of two or more separate emission channels is separated by the splitting system into two or more beams that travel along separate paths so that each beam reaches a different detector in the array of detectors. Each beam is a different emission channel and the beams are substantially parallel.

Microscopy instruments with beam splitting system including optical filters and mirrors

Various light-scanning systems that can be used to perform rapid point-by-point illumination of a focal plane within a specimen are disclosed. The light-scanning systems can be incorporated in confocal microscopy instruments to create an excitation beam pivot axis that lies within an aperture at the back plate of an objective lens. The light-scanning systems receive a beam of excitation light from a light source and direct the excitation beam to pass through the pivot point in the aperture of the back plate of the objective lens while continuously scanning the focused excitation beam across a focal plane.

Light-scanning systems

Various beam selectors for selectively placing one of at least two beams of light along the same output path are disclosed. In one aspect, a beam selector receives at least two substantially parallel beams of light. The beam selector includes a plate with an aperture so that when one of the at least two beams is selected for transmission, the beam selector directs only the selected beam along an output path through the aperture. The plate can also serve to block transmission of unselected beams. The output path through the aperture is the same for each of the at least two beams when each beam is selected. Beam selectors can be incorporated into fluorescence microscopy instruments to selectively place particular excitation beams along the same path through the microscope objective lens and into a specimen to excite fluorescence of fluorescent probes attached to a particular component of the specimen.

Laser beam selectors

Methods and systems to resolve positions of sample components in fluorescence stochastic microscopy using three-dimensional structured illumination microscopy ('3D-SIM') are disclosed. In one aspect, components of a sample specimen are labeled with fluorophores and weakly illuminated with a frequency of light to stochastically convert a subset of the fluorophores into an active state. The sample is then illuminated with a three-dimensional structured illumination pattern ('3D-SIP') of excitation light that causes the activated fluorophores to fluoresce. As the 3D-SIP is incrementally moved within the volume of the sample and images are recorded, computational methods are used to process the images to locate and refine the locations of the activated fluorophores thereby generating a super-resolution image of sample components.

Methods for resolving positions in fluorescence stochastic microscopy using three-dimensional structured illumination

Fluorescence microscopy systems with polychroic mirror changers are described. In one aspect, a polychroic mirror changer includes a polychroic-mirror array. The array includes a plate with a planar surface and a number of holes formed in the plate. The array also includes polychroic mirrors attached to the planar surface of the plate such that each polychroic mirror covers one of the holes and the reflective surface of each polychroic mirror is adjacent to and aligned with the planar surface of the plate. Each polychroic mirror is partially exposed through a corresponding hole to reflect a different subset of excitation channels of a beam of excitation light input to the changer. The polychroic-mirror array can be mounted in the changer so that when a different subset of excitation channels is selected to illuminate a specimen, the plate is moved within a single plane of motion.

Fluorescence microscopes with polychroic mirror changers

Illumination system for a microscope system capable of being mode-switchable between a first and a second illumination mode, comprising one source of light for providing a collimated beam of light, at least one selector mirror capable of being positioned in at least two positions to redirect the beam of light in two different beam paths, the first beam path being a direct exit beam path wherein the selector mirror redirects the beam of light along an exit beam path to provide a first illumination mode, the second beam path is a mirror loop path comprising two or more mirrors arranged to redirect the beam of light onto the selector mirror such that it is redirected by the selector mirror a second time along the exit beam path, and wherein mirror loop path comprises at least one optical element arranged to optically alter the beam of light to provide the second illumination mode. According to one embodiment, the first illumination mode is Total Internal Reflection (TIRF) and the second illumination mode is Photokinetics (PK) illumination.

Mode-switchable illumination system for a microscope

Illumination phase controls that provide precise and fast phase control of structured illumination patterns used in structure illumination microscopy are described. A coherent light source is used to generate a beam of coherent light that is split into at least three coherent beams of light. In one aspect, an illumination phase control is composed of at least one pair of rotatable windows to apply at least one phase shift to at least one of the beams. An objective lens is to receive the beams and focus the at least three beams to form an interference pattern. The phase control can be used to change the position of the interference pattern by changing the at least one phase shift applied to the at least one beam.

Systems and methods for illumination phase control in fluorescence microscopy

Various superimposing beam controls that can superimpose beams of light with different optical properties are described. In one aspect, a beam control receives a beam of light and outputs one or more beams. Each beam is output in a different polarization state and with different optical properties. Superimposing beam controls can be incorporated in fluorescence microscopy instruments to split a beam of excitation light into one or more beams of excitation light. Each beam of excitation light has a different polarization and is output with different optical properties so that each excitation beam can be used to execute a different microscopy technique.

Systems for fluorescence illumination using superimposed polarization states

Irradiance control systems ('ICSs') that control the irradiance of a beam of light are disclosed. ICSs include in a beam translator and a beam launch. The beam translator translates the beam substantially perpendicular to the propagating direction of the beam with a desired displacement so that the beam launch can remove a portion of the translated beam and the beam can be output with a desired irradiance. The beam launch attenuates the irradiance of the beam based on the amount by which the beam is translated. ISCs can be incorporated into fluorescent microscopy instruments to provide high-speed, fine-tune control over the irradiance of excitation beams.

Laser beam irradiance control systems

Various embodiments of the present invention are directed to optical-fiber-based light sources for use in microscopy, spectrometry, and other scientific and technical instruments, devices, and processes. Light-emitting diodes ('LEDs') and other light sources are, in various embodiments of the present invention, incorporated on or within an optical fiber or fiber-optic cable in order to produce a bright optical-fiber-based light source. By incorporating light-emitting devices on or within an optical fiber, a significantly greater photon flux can be obtained, within the optical fiber or fiber-optic cable, than can be obtained by directing light from equivalent, external light-emitting elements into the optical fiber or fiber-optic cable, and the optical-fiber-based light sources of the present invention provide desirable characteristics of the light sources embedded on or within them.

Growing community of inventors

Issaquah, WA, United States of America

Jeremy R Cooper