Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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 trip

Abstract: Embodiments of the present invention are directed to providing and controlling illumination for three-dimensional structured illumination microscopy. Three phase-coherent beams, referred to as a “beam triplet,” are produced with planar beamsplitters. The relative phases of the beams are controlled by piezo-coupled mirrors or other means. The beams pass through the microscope objective and interfere to produce the 3D structured illumination pattern. The spatial orientation and location of the pattern is manipulated by adjusting the relative phases of the beams.

Abstract: 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.

Abstract: The present invention provides a magnetic resonance force microscopy apparatus and method for use in combination with an oscillator. The oscillator has a motional body and one member of a sample/magnet pair is disposed on the motional body. The present invention actuates the motional body. The apparatus comprises a holder adapted to mount the second member of a sample/magnet pair, an RF field generator positioned to apply a field to the sample, a motion sensor adapted to be coupled with the motional body, an actuator adapted to be coupled with the motional body, and a motion controller coupled with the actuator and with the motion sensor.