University of Notre Dame Du Lac

Cornell University

Indiana Integrated Circuits, LLC

Scott Howard

Gary H Bernstein

Jason M Kulick

Douglas C Hall

Anthony Hoffman

Yide Zhang

Watt W Webb

Douglas Scherr

Chunhui (Chris) Xu

Dimitre Gueorguiev Ouzounov

Cody J Smith

Genevieve Vigil

David R Rivera

Christopher M Brown

Demirhan Kobat

David Huland

One aspect of the present disclosure relates to systems and methods that can be used for super-sensitivity multiphoton frequency-domain fluorescence lifetime imaging microscopy (MPM-FD-FLIM). One or more laser light sources can deliver excitation light with an intensity modulated by a periodic function to a sample, which includes a fluorophore concentration. A receiver can receive a fluorescence signal emitted from the fluorophore concentration over a time period. A computing device can transform the fluorescence signal to the frequency domain and measure a fluorescence lifetime associated with the sample in the frequency domain based on a DC component and at least one higher harmonic component generated by non-linear optical mixing of the modulated excitation light. Using the DC component and the at least one higher harmonic component can increase the sensitivity of an image created by the MPM-FD-FLIM system.

Super-sensitivity multiphoton frequency-domain fluorescence lifetime imaging microscopy

A microscopy method and system includes obtaining a plurality of raw fluorescence images, respective ones of the plurality of raw fluorescence images obtained by exciting a sample using a light source at a respective irradiance value in a weak saturation region of the sample, and capturing the respective raw fluorescence image; applying a plurality of weights to the plurality of raw fluorescence images in a one-to-one correspondence so as to generate a plurality of weighted fluorescence images, wherein a respective weight is based on the respective irradiance value at which the corresponding raw fluorescence image was obtained; and linearly combining the plurality of weighted fluorescence images, thereby generating the output image having a resolution greater than a diffraction limit. Respective raw fluorescence images correspond to irradiance values different from one another.

Super-resolution fluorescence microscopy by stepwise optical saturation

First, second, and third integrated devices each include one or more interconnecting structure. Each interconnecting structure includes (i) one or more interconnecting nodules extending from an edge surface of the device, (ii) one or more interconnect voids formed in an edge surface of the device, or (iii) both (i) and (ii). The one or more interconnecting structures on each of the first and second device is mated with the one or more interconnecting structures on the second device. The first integrated device includes a signal output, the third integrated device includes a signal input; and the second integrated device includes a conductor for conducting a signal from the signal output to the signal input.

Inter-chip alignment

First and second integrated devices each have an optical component and a plurality of interconnect structures disposed one edge thereon. The first edge surface of the second integrated device is positioned contiguous to the first edge surface of the first integrated device. The interconnect structures disposed on the first integrated device are in physical contact with the interconnect structures disposed on the edge surface of the second integrated device so as to provide alignment for conveying at least one signal between the optical components on the first and second integrated devices.

Quilt packaging system with mated metal interconnect nodules and voids

Quilt packaging system with interdigitated interconnecting nodules for inter-chip alignment

An optical scanner, scanner apparatus, or scanner assembly, which may be particularly advantageous for use in a multiphoton microscope, includes a first drivable bending component, a second drivable bending component mounted perpendicularly to the first component, and at least one optical waveguide coupled one or both of the first and second bending components, wherein the at least one optical waveguide provides both a propagation path for a multiphoton excitation radiation delivery between a light source and a target and a multiphoton-induced emission radiation delivery between the target and a detector. A GRIN relay lens. A multiphoton microscope incorporating the scanner and the GRIN relay lens.

Multi-path, multi-magnification, non-confocal fluorescence emission endoscopy apparatus and methods

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South Bend, IN, United States of America

Scott Howard