Photostable Nanoparticle Calibration Phantom for Optical Imaging
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Solution Overview
Problem
Multimodal optical microscopy systems face challenges in longitudinal measurements due to the rapid bleaching of fluorescent beads, making it difficult to compare system performance over time or between different systems.
Innovation Solution
A calibration phantom with optically transparent contrast layers and a localizing grid layer, featuring nanoparticles with unique optical signatures, such as nanodiamonds, that remain photostable and provide fixed reference points for reliable imaging across multiple sessions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescent beads are used for calibration, then sub-resolution point source quality is improved, but photostability deteriorates due to rapid bleaching
Solution Approach 1:
The patent changes the material parameter of the calibration beads from fluorescent materials to non-fluorescent scattering materials (such as polystyrene or silica beads). This parameter change eliminates the photobleaching issue while maintaining the sub-resolution point source quality needed for optical system characterization.
Solution Approach 2:
The patent replaces long-lived fluorescent beads with short-lived fluorescent excitation but long-lasting structural scattering beads. The scattering beads themselves are photostable and do not bleach, providing a permanent reference that can be imaged repeatedly without degradation.
2Use of energy by moving object
If fluorescent beads are used for calibration, then excitation efficiency assessment is improved, but longitudinal measurement capability deteriorates due to intensity drop
Solution Approach 1:
The patent separates the calibration function into two distinct components: fluorescent beads for excitation efficiency assessment and non-fluorescent scattering beads for longitudinal position reference. This segmentation allows each component to optimize its specific function without the limitations of the other.
Solution Approach 2:
The patent introduces non-fluorescent scattering beads as an intermediary reference that mediates between the fluorescent excitation assessment and the longitudinal measurement requirements. These beads serve as a stable mediator that does not bleach, enabling continuous tracking.
3Measurement precision
If fluorescent beads are used for system evaluation, then optical performance assessment is improved, but comparability between systems deteriorates due to bleaching variability
Solution Approach 1:
The patent changes the material composition parameter of the calibration reference from fluorescent materials to photostable scattering materials. This parameter change ensures that the reference objects maintain their optical properties across different systems and time points, enabling reliable comparability.
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 stable and repeatable characterization of multimodal optical imaging systems, allowing for quantitative assessment and optimization, and providing a photostable target for extended periods, thus overcoming the limitations of fluorescent beads.
Implementation Method 1
nanoparticles arranged on a surface of the layer
Implementation Method 2
nanoparticles arranged on a surface of the layer
Implementation Method 3
Each contrast layer is composed of an optically transparent material
Data Source
AI summary
A calibration phantom, or related nanoparticle substrate, for multimodal optical system characterization includes a contrast layer and a localizing grid layer. The contrast layer may be a two-dimensional (2D) layer, a stack of 2D layers, a three-dimensional (3D) block, or combinations thereof. Nanoparticles are arranged on, embedded in, or coupled to the contrast layer(s). Nanoparticles provide sub-resolution point-sources that can provide optical contrast for multiple different imaging modalities. The localizing grid layer includes a grid, which may be etched in, or otherwise marked on, the localizing grid layer. By coupling the contrast layer to the localizing grid layer, the positions of the nanoparticles remain fixed relative to the localizing grid, which can be visualized by the imaging system. In this way, a reliable and repeatably imageable calibration phantom is provided.