Spherical Sample Chamber for Aberration-Free Microscopy
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Solution Overview
Problem
Conventional methods for microscopic imaging of cleared samples, such as brains, face challenges due to aggressive and toxic clearing chemicals, which can damage optical components and cause imaging aberrations, and require complex handling to achieve deep penetration and high-quality imaging.
Innovation Solution
A sample chamber with a spherical outer side and a detection axis that can be rotated or pivoted relative to the sample chamber, combined with non-diffractive light sheet illumination and adaptive optical elements, allows for controlled imaging of large samples by maintaining a constant detection axis orientation and reducing aberrations through multi-view fusion and plenoptic detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional immersion arrangements are used with clearing media, then deep penetration and high-quality imaging can be achieved, but optical components are damaged by aggressive and toxic chemicals
Solution Approach 1:
The system is divided into two separate chambers: a first sample chamber containing the clearing media and sample, and a second sample chamber containing the objective lens and immersion media. This segmentation prevents direct contact between aggressive clearing chemicals and optical components while maintaining imaging quality through the second chamber.
Solution Approach 2:
A wall with optical properties (transparent or translucent) acts as an intermediary between the first sample chamber and second sample chamber. This wall allows illumination and detection radiation to pass through while physically isolating the objective lens from toxic clearing media, protecting optical components without compromising imaging function.
2Length of stationary object
If clearing media is used for deep penetration imaging, then effective penetration depth is increased, but imaging aberrations occur due to unknown or uncompensated optical properties
Solution Approach 1:
The imaging system is segmented into two chambers with different optical media. The first chamber uses clearing media for deep penetration, while the second chamber uses immersion media with known and compensated optical properties (refractive index, Abbe number) that match the objective lens, thereby eliminating imaging aberrations.
Solution Approach 2:
The system changes the optical parameters of the media in different chambers. The second chamber employs immersion media with specifically selected refractive index and Abbe number that are compensated for in the objective lens design, ensuring high imaging accuracy while the first chamber uses clearing media for deep penetration.
3Measurement precision
If clearing chemicals are used for sample preparation, then structural visibility is improved, but occupational safety and health protection requirements increase
Solution Approach 1:
The system segments hazardous clearing chemicals into a sealed first sample chamber isolated from the operator environment. The wall between chambers contains the chemicals while allowing optical transmission, thereby maintaining structural visibility benefits while reducing safety system complexity through engineered containment rather than extensive safety protocols.
4Device complexity
If conventional sample chambers are used, then simple structure is maintained, but imaging of large samples at multiple angular positions is difficult
Solution Approach 1:
The first sample chamber employs a spherical or curved wall design instead of conventional flat chambers. This curved geometry enables the chamber to be rotated and positioned at multiple angular orientations while maintaining optical access and structural integrity, facilitating imaging of large samples from different angles without requiring complex multi-chamber systems.
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
This configuration enables high-quality imaging of large samples with reduced aberrations and increased penetration depth, allowing for comprehensive visualization of cleared samples while protecting optical components from aggressive chemicals and improving imaging efficiency.
Implementation Method 1
The outer side of the wall has the shape of a spherical segment... the sample chamber and the detection axis are rotated and/or pivoted relative to one another... The detection axis always extends through the spherical outer side
Implementation Method 2
The illumination beam path is directed through the outer side and into the sample space... the illumination beam path is directed through the outer side and into the sample space
Implementation Method 3
detection radiation, which was caused by means of illumination radiation directed into the sample space along the illumination axis, is captured along a detection axis
Data Source
AI summary
A sample chamber encloses a sample space for positioning a sample and includes a wall that delimits the sample space and has an outer side facing away from the sample space. An illumination beam path is directed through the outer side into the sample space. Detection radiation is detected along a detection axis extending from the sample chamber through the wall of the sample chamber. The sample chamber has an outer surface with a shape of a spherical section with a circular disc as the base surface. The sample chamber and the detection axis are rotated and/or pivoted relative to one another about the center point of the circular disc so that different angular positions of the sample chamber relative to the detection axis are adjusted and image data is recorded at different angular positions of the sample chamber relative to the detection axis.