Systems and methods for improved light-sheet microscopy
Inventors
Assignees
Case Western Reserve University
Publication Number
US-12253469-B2
Publication Date
2025-03-18
Expiration Date
2040-07-16
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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.
Core Innovation
The invention provides systems and methods for improved light-sheet microscopy by innovatively employing cost-effective and simplified components that address key limitations in traditional light-sheet microscopy systems. Central to the disclosure is the integration of a voice coil motor (VCM) with a focusing lens in the light focusing system to increase the imagable field of view. The VCM enables movement of the lens along the axis of the light beam, allowing easy adjustment of the light sheet's position within the focal plane and thus extending the field of view without the expense and complexity associated with traditional scanning mechanisms.
The light generation system is enhanced by using a multimode laser diode, which generates a light beam with a high order Hermite-Gaussian mode. This configuration improves the uniformity of the beam profile and increases usable optical power. Unlike conventional systems that require expensive single mode lasers and additional components to modify beam profiles, the multimode laser diode inherently provides ellipticity and a wider, flatter intensity profile desirable for light-sheet microscopy, thereby reducing costs and simplifying the light path.
In the imaging system, a fluid chamber featuring a positive cylindrical optical window is employed to minimize spherical aberrations during image acquisition. By placing a translucent biological sample within this chamber, and aligning the optical properties among the sample, medium, and cylindrical window, the system ensures improved optical resolution while maintaining a compact and cost-effective design. This method permits the use of high numerical aperture lenses to achieve a thinner light sheet and higher imaging resolution without the complexity or cost typical of existing solutions.
Claims Coverage
There are three main inventive features described in the independent claims of this patent.
Multimode laser diode with high order Hermite-Gaussian mode for light generation
A light generation system utilizing a multimode laser diode configured to output a light beam with a high order Hermite-Gaussian mode, where one dimension of the beam profile has a Hermite-Gaussian index equal to zero and the other greater than zero, with the zero index dimension exhibiting higher output divergence. The collimated light beam is produced using a collimating lens. This configuration increases uniformity of the beam profile and provides higher usable optical power for light-sheet microscopy.
Voice coil motor-driven focusing lens for extended field of view
A light focusing system comprising a focusing lens—specifically a cylindrical or acylindrical lens—attached to a voice coil motor (VCM) that moves the lens along the axis of the collimated light beam, including by vibrating at rates from 10 Hz to 100 Hz. This motion changes the position of the light sheet within the imaging device's focal plane, allowing the focal sheet to achieve a wide and flat beam profile at the center, which corresponds to an increased field of view.
Fluid chamber with positive cylindrical optical window to minimize spherical aberrations
An imaging system incorporating a fluid chamber containing a positive cylindrical optical window attached directly to the chamber's exterior. The cylindrical window is designed so the distance between the sample and the focusing lens is reduced by a factor of 1.25 compared to traditional systems. This configuration minimizes spherical aberrations when focusing a collimated light beam into a thin light sheet for imaging translucent biological samples, thus achieving higher resolution and a more compact system.
Method for light-sheet microscopy using these components
A method includes obtaining a translucent biological sample, immersing it in a medium, and placing it in a fluid chamber with a positive cylindrical optical window and sample holder. A collimated light beam is generated by a multimode laser diode with the described Hermite-Gaussian mode. The beam is focused by a cylindrical or acylindrical lens to create a thin light sheet passing through the optical window and sample. The system minimizes spherical aberration and permits imaging at a reduced sample-to-lens distance.
In summary, the inventive features revolve around the use of a multimode laser diode for improved light generation, a VCM-driven focusing lens for expanded imaging area, and a fluid chamber with a positive cylindrical optical window for minimizing aberrations. These elements collectively offer simplified, cost-effective, and high-performance solutions for light-sheet microscopy.
Stated Advantages
The systems and methods reduce the expense and complexity of light-sheet microscopy, making it more accessible for widespread use.
The voice coil motor-driven lens enables a larger imagable field of view in a simplified and cost-effective manner without sacrificing high resolution.
Using a multimode laser diode increases uniformity of the beam profile and allows for higher usable optical power, eliminating the need for extra post-processing and reducing system size.
The fluid chamber with a positive cylindrical optical window minimizes spherical aberrations and enables higher resolution imaging with thinner light sheets.
Combining the disclosed improvements results in a light-sheet microscope with extended focal plane, uniform beam profile, higher optical power, higher resolution, and a more compact, cost-effective system.
Documented Applications
3D fluorescence imaging of biomedical samples using light-sheet microscopy.
High-resolution imaging of translucent biological samples, such as optically cleared tissue or naturally translucent tissue.
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