Solid Immersion Lens Super Resolution Microscopy
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Solution Overview
Problem
Current super-resolution microscopy techniques face limitations in achieving sub-100 nm resolution for both fluorescent and non-fluorescent specimens, often requiring complex instrumentation and fluorescence-based methods, which hinder practical application in biomedical research and diagnosis.
Innovation Solution
The use of high refractive index solid-immersion lenses (SIL) with unique light transmission optics allows for sub-nanometer resolution imaging by exploiting total internal reflection effects at the interface between the SIL and a sample medium, enabling transmission mode microscopy that can image non-fluorescent specimens and utilizing fiducial markings for enhanced imaging capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional diffraction-limited microscopy is used, then the system is simple and easy to operate, but the resolution is limited to approximately 200 nm
Solution Approach 1:
The patent changes the refractive index parameter by introducing a solid immersion lens with high refractive index material, which shortens the effective wavelength of light and increases the numerical aperture, thereby improving resolution beyond the conventional diffraction limit without requiring complex fluorescence-based instrumentation
Solution Approach 2:
The patent uses the specimen itself as a local high-refractive index region, eliminating the need for fluorescence labeling copies and enabling direct imaging of non-fluorescent specimens with super-resolution
2Measurement precision
If fluorescence-based super-resolution methods are used, then resolution improves to 100 nm to 15 nm, but the requirement for fluorescence labeling and complex instrumentation increases
Solution Approach 1:
The specimen's own refractive index properties are utilized to create the high-refractive index regions needed for super-resolution imaging, eliminating the need for external fluorescence labeling and complex fluorescence microscopy instrumentation
Solution Approach 2:
The patent replaces complex fluorescence-based optical systems with a simpler solid immersion lens system that uses total internal reflection and refraction physics to achieve super-resolution
3Measurement precision
If fluorescence labeling is used for super-resolution imaging, then resolution improves, but specimen damage increases and applicability to non-fluorescent specimens is limited
Solution Approach 1:
The specimen's inherent refractive index is used to generate the optical effects needed for super-resolution imaging, eliminating the need for fluorescence labeling and reducing specimen damage from labeling chemicals and intense excitation light
Solution Approach 2:
The patent converts the specimen's natural refractive index properties, which would normally cause refraction and reflection losses, into a beneficial effect by using the specimen itself as the high-refractive index region for super-resolution imaging
4Measurement precision
If high refractive index solid-immersion lenses are used, then resolution improves beyond the diffraction limit, but the complexity of achieving and maintaining contact between the SIL and specimen increases
Solution Approach 1:
The patent moves the high-refractive index region to the specimen side rather than requiring precise SIL-specimen contact, effectively changing the dimensional arrangement to eliminate alignment complexity while maintaining super-resolution capability
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 approach enables imaging at resolutions finer than 100 nm, including non-fluorescent specimens, with reduced complexity and fluorescence labeling, improving signal strength and minimizing specimen damage, thus enhancing biomedical research and diagnostic capabilities.
Implementation Method 1
The high index of the SIL effectively shortens the wavelength of the incident light used for observation, resulting in an increased numerical aperture and better resolution
Implementation Method 2
Exploiting these transmission effects allows for limits of resolution in the nanometer to sub-nanometer range... only incident light which contacts the features of interest that act as local-high refractive index regions is transmitted through the SIL (e.g. due to scattering of the incident light by the features of interest), while any light which does not come into contact with the feature of interest is internally reflected
Implementation Method 3
only incident light which contacts the features of interest that act as local-high refractive index regions is transmitted through the SIL (e.g. due to scattering of the incident light by the features of interest)
Data Source
AI summary
Described herein are methods and systems for the optical imaging of a physical specimen of interest that is in contact with, or in close proximity to, the backplane of a high refractive index solid-immersion lens (SIL), wherein the specimen comprises features of interest that act as a local high-refractive index regions. The SIL lens preferably comprises fiducial markers.