Multiscale Light-Sheet Microscopy for High-Resolution Live Imaging
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Solution Overview
Problem
Current biological live imaging techniques face challenges in achieving high spatial and temporal resolution while minimizing photo-damage, often requiring the observation of large specimens to be reduced to small functional subunits for study, which limits the understanding of complex biological dynamics.
Innovation Solution
A microscope system that utilizes a spatial adjustment apparatus to produce and direct light sheets with different spatial statuses, allowing for multiscale imaging by switching between large and small field of views, enabling high-resolution imaging of cellular structures and neuronal activity with minimal photo-bleaching and photo-toxic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If a thin light sheet is used for illumination in light-sheet imaging, then photo-bleaching and photo-toxic effects are minimized, but spatial resolution and imaging speed are limited
Solution Approach 1:
The patent divides the illumination into multiple thin light sheets that are scanned across the specimen in steps, allowing each light sheet to provide minimal photo-damage while collectively achieving high spatial resolution through sequential illumination of multiple sections
Solution Approach 2:
The patent transitions from point illumination to sheet illumination by adding a spatial dimension, where the light sheet extends perpendicular to the detection axis, enabling volumetric imaging with reduced photo-damage while maintaining high spatial resolution through the extended illumination geometry
2Area of stationary object
If the entire specimen is illuminated to capture large-scale structures, then field of view is improved, but photo-damage increases
Solution Approach 1:
The patent segments the illumination into multiple thin light sheets that scan across different regions of the specimen, allowing the entire specimen to be imaged through sequential illumination of multiple sections rather than simultaneous illumination of the entire volume
Solution Approach 2:
The patent employs periodic scanning of the light sheet across the specimen in steps along the detection axis, where the light sheet is periodically repositioned to illuminate different regions, enabling complete specimen imaging through repeated cyclic illumination sequences
3Measurement precision
If high spatial resolution is achieved by reducing observation to small functional subunits, then imaging precision is improved, but the ability to study complex biological dynamics is limited
Solution Approach 1:
The patent segments the illumination into multiple thin light sheets that can be independently positioned and scanned, allowing high spatial resolution imaging of specific subunits while maintaining the capability to image the entire specimen by coordinating multiple segments
Solution Approach 2:
The patent adds a spatial dimension to illumination by using extended light sheets perpendicular to the detection axis, enabling simultaneous capability to image both small subunits with high resolution and large specimens through volumetric scanning
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables fast, three-dimensional imaging of biological specimens with excellent signal-to-noise ratio and millisecond temporal resolution, allowing for the capture of fine details and large-scale structures without forcing a trade-off between spatial resolution and field of view.
Implementation Method 1
collecting the resulting fluorescence emitted from the specimen region due to an interaction between a specimen at the specimen region and a light sheet
Data Source
AI summary
A microscope system includes at least one illumination subsystem configured to produce and direct a light sheet toward a specimen region. The illumination subsystem includes a spatial adjustment apparatus configured to operate in a plurality of different modes, each operating mode configured to produce a light sheet having a different spatial status. The microscope system includes at least one detection subsystem arranged to collect fluorescence emitted from the specimen region due to an interaction between a specimen at the specimen region and a light sheet. The at least one detection subsystem includes a plurality of imaging devices, with each imaging device being associated with a different spatial status such that each imaging device is configured to record images of the fluorescence due to an interaction between a specimen at the specimen region and the light sheet of the associated spatial status.