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US 12,253,469 B2Granted
Systems and methods for improved light-sheet microscopy
AssigneeCase Western Reserve University
InventorsYehe Liu, Michael Jenkins
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Abstract
Described herein are systems and methods for improving light-sheet microscopy with cost-effective and simplified components. Such cost-effective and simplified components can be implemented in a light focusing system, a light generation system, and/or in imaging system. The light focusing system can be improved by attaching a voice coil motor to a focusing lens to increase the imagable field of view. The light generation system can be improved with a multimode laser diode to increase the uniformity of the beam profile and to increase the usable optical power. The imaging system can be improved by using a fluid chamber with positive cylindrical optical window for minimizing spherical aberrations.
Claims24
A system that facilitates light-sheet microscopy comprising:
- a light generation system consisting essentially of:
- a multimode laser diode configured to output a light beam with a high order Hermite-Gaussian mode, wherein a Hermite polynomial of a Gaussian function of a beam profile of the light beam has a Hermite-Gaussian index equal to zero in one dimension and greater than zero in another dimension, wherein the one dimension with the index equal to zero has a higher output divergence than the other dimension;
- a collimating lens configured to collimate the light beam;
- a light focusing system comprising:
- a focusing lens configured to focus the collimated light beam into a focal sheet within a focal plane of an imaging device by achieving a wide and flat beam profile at a center of the light beam corresponding to a field of view, wherein the focal sheet is a light sheet, wherein the focusing lens is configured to focus the light beam in the one dimension that the Hermite-Gaussian index equal to zero has a higher output divergence, wherein the focusing lens is a cylindrical lens or an acylindrical lens;
- and
- a voice coil motor (VCM) attached to the focusing lens and configured to move the focusing lens along an axis of the light beam by vibrating at a rate of 10 Hz to 100 Hz, causing a change in a position of the light sheet within the focal plane of the imaging device;
- and
- a fluid chamber configured to immerse a sample in a medium and configured to receive a focused and collimated light beam, the fluid chamber comprising:
- a sample holder configured to secure the sample immersed in the medium in the fluid chamber;
- and
- a positive cylindrical optical window attached directly to an outside of the fluid chamber, wherein the distance between the sample and the focusing lens is reduced by a factor of 1.25 compared to traditional light sheet microscopy.
9 more elements
A method comprising:
- obtaining a translucent biological sample;
- immersing the translucent biological sample in a medium;
- placing the translucent biological sample immersed in the medium within in a fluid chamber of a microscope, the fluid chamber comprising:
- a positive cylindrical optical window attached directly to an outside of the fluid chamber, and
- a sample holder configured to secure the translucent biological sample immersed in the medium in the fluid chamber;
- generating, by a light generation system, a collimated light beam that is focused in a direction of the fluid chamber, wherein the light generation system comprises:
- a multimode laser diode configured to output a light beam with a high order Hermite-Gaussian mode, wherein a Hermite polynomial of a Gaussian function of a beam profile of the light beam has an index equal to zero in one dimension and greater than zero in another dimension, wherein the one dimension with the index equal to zero has a higher output divergence than the other dimension, and
- a collimating lens configured to collimate the light beam;
- and
- focusing, by a cylindrical lens or an acylindrical lens, the collimated light beam in the one dimension to pass through the positive cylindrical optical window as a thin light sheet that is located within the translucent biological sample, wherein the cylindrical lens or the acylindrical lens focuses the collimated light beam into a focal sheet within a focal plane of an imaging device by achieving a wide and flat beam profile at a center of the light beam corresponding to a field of view, wherein the focal sheet is a light sheet,
- wherein the thin light sheet passing through the positive cylindrical optical window minimizes spherical aberrations, and
- wherein the distance between the sample and the cylindrical lens or the acylindrical lens is reduced by a factor of 1.25 compared to traditional light sheet microscopy.
9 more elements
Dependencies are inferred from the claim text.