Ge Healthcare Bio-sciences Corp.

General Electric Company

Applied Precision, Inc.

William Michael Dougherty

Steven A Reese

Jeremy R Cooper

Paul Carlyle Goodwin

David A Stewart

David Edward Stewart

Steven Charles Quarre

David Stewart

Methods and apparatus are described for delivering index-matching immersion liquid in high numerical-aperture optical microscopy and lithography. An array of immersion liquid droplets is delivered to a specimen substrate or specimen substrate cover by an immersion liquid printing apparatus. An immersion liquid reservoir provides immersion liquid to the printer by a precision pump. The printer delivers immersion liquid to the substrate or substrate cover in arrays of immersion liquid droplets of defined volumes and array patterns. The volumes and patterns of array droplets delivered to the substrate or substrate cover are optimized to maintain adequate immersion liquid between the substrate or substrate cover and an immersion objective while avoiding the formation of air bubbles in the immersion liquid and the accumulation of excess volumes of immersion liquid.

Dispersing immersion liquid for high resolution imaging and lithography

An optical microscope and method for detecting lens immersion in optical microscopy includes an ultrasound circuit acoustically coupled to both an objective lens and a sample of an optical microscope, the ultrasound circuit comprising an ultrasound transmitter and an ultrasound receiver. The optical microscope and method includes transmitting an ultrasound pulse from the ultrasound transmitter to the ultrasound receiver, determining that a transit time of the ultrasound pulse is less than a threshold time, and providing an output signal from the pulse discriminator indicating that the ultrasound pulse is less than the threshold time.

Optical microscope and method for detecting lens immersion

An optical microscope and method for detecting lens immersion in optical microscopy includes an ultrasound circuit acoustically coupled to both an objective lens and a sample slide of an optical microscope, the ultrasound circuit comprising an ultrasound transmitter and an ultrasound receiver. The optical microscope and method includes transmitting an ultrasound pulse from the ultrasound transmitter to the ultrasound receiver, determining that a transit time of the ultrasound pulse is less than a threshold time, and providing an output signal from the pulse discriminator indicating that the ultrasound pulse is less than the threshold time.

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

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

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

The approach of one embodiment of the present invention is to mechanically vibrate a length of fiber optic cable transmitting coherent laser light, so that a mechanical resonance in the optical fiber is excited. This is achieved by suspending the fiber optic cable between two points and controlling both the axial tension on the suspended fiber optic cable as well as the mechanical forcing frequency. The cyclic, high-frequency mechanical perturbations of the fiber rapidly vary the path length and internal reflection angles of one or more respective modes of the transmitted laser light. In certain embodiments, the system may be tuned to induce a standing mechanical wave in the fiber. Higher-harmonic waveforms and higher amplitudes in the resonant fiber produce excellent speckle reduction and uniform intensity distributions.

Uniform light source for an imaging instrument

A structured-illumination module included in a 3D-structured-illumination-based fluorescence microscope, the structured-illumination module comprising: a structured-illumination-module frame; a beam-alignment module including a central tilt mirror coupled to an underside of a top horizontal plate of the structured-illumination-module frame; a set of directional mirrors, one of which receives, at a given point in time, input, polarized, coherent light reflected from the central tilt mirror; three sets of beam splitters, on three arms of the structured-illumination-module frame, the each splits an incident illumination beam, reflected to the set of beam splitters from a directional mirror of the set of directional mirrors, into a coherent beam triplet; and a phase-shift module that receives a beam triplet, at a given point in time, generated by one of the sets of beam splitters and reflected from the beam-alignment module and that introduces a desired relative phase relationship among the beams of the beam triplet.

Growing community of inventors

Issaquah, WA, United States of America

William Michael Dougherty