Multilayer Fluorescent Nanoparticles for Intracellular Imaging
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Solution Overview
Problem
Current multiplex coding technologies face challenges with large particle sizes, which hinder their application in intracellular imaging due to size limitations and issues with fluorescence signal brightness and noise, particularly for particles above 100 nm.
Innovation Solution
Development of multilayer, fluorescently responsive silica nanoparticles with sizes below 100 nm, incorporating three spectrally distinct dyes at multiple intensity levels, where dyes are added in a layer-by-layer fashion with silica shells to minimize energy transfer and maximize brightness, allowing for intracellular bioimaging and high-throughput screening.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Illumination intensity
If large particle sizes (>100 nm) are used for multiplex coding, then fluorescence signal brightness can be maintained, but intracellular imaging capability is lost due to size limitations
Solution Approach 1:
The patent segments the particle structure into multiple functional layers: a core containing fluorescent dyes, intermediate silica shells for spatial separation, and an outer PEG layer for biocompatibility. This segmentation allows the particle to maintain small overall size (<100 nm) for cellular uptake while concentrating fluorescent dyes in the core to achieve high brightness
Solution Approach 2:
The patent implements a nested structure where fluorescent dyes are embedded in the core, which is then enclosed by silica shells, which are in turn covered by PEG layers. This nested architecture maximizes the use of internal space, allowing high dye loading density within the small particle volume while maintaining the size constraint for intracellular imaging
2Quantity of substance
If multiple dyes are incorporated into particles to achieve multiplex coding, then coding capacity increases, but fluorescence signal quality deteriorates due to energy transfer and quenching
Solution Approach 1:
The patent introduces silica shells as intermediary layers between different fluorescent dyes. These silica layers act as physical barriers that prevent direct energy transfer and quenching interactions between dyes, allowing multiple dyes to be incorporated at high concentrations while maintaining individual fluorescence signals for multiplex coding
Solution Approach 2:
The patent applies local quality by creating regions of high dye concentration in the core while separating different dye types with silica shells. This allows each dye to maintain its optimal fluorescence properties locally while the overall particle achieves high coding capacity through the combination of multiple dyes
3Length of moving object
If small particle sizes (<100 nm) are used for intracellular imaging, then cellular uptake is enabled, but fluorescence signal brightness decreases
Solution Approach 1:
The patent creates a composite material structure combining fluorescent dyes, silica shells, and PEG polymers. This composite architecture allows the particle to achieve small size for cellular uptake while the high-density packing of fluorescent dyes in the core compensates for the reduced volume, maintaining high fluorescence signal brightness
Solution Approach 2:
The patent changes the concentration parameter of fluorescent dyes within the particle core, achieving ultra-high dye loading densities. This parameter change compensates for the small particle volume, ensuring sufficient fluorescence signal brightness while maintaining the <100 nm size required for intracellular imaging
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
The nanoparticles achieve one to three orders of magnitude fluorescence brightness enhancement, enabling effective intracellular imaging and multiplexing with improved signal-to-noise ratios, suitable for in vivo and in vitro applications.
Implementation Method 1
dyes are added in a layer-by-layer fashion with silica shells to minimize energy transfer and maximize brightness
Implementation Method 2
multicolor fluorescent silica nanoparticles... with sizes below 100 nm that contain two, three or more spectrally distinct dyes at two, three or more different intensity levels
Data Source
Figure 1a~1c
Figure 2a~2c
Figure 2d~2f
AI summary
A multilayer, fluorescently responsive material (FRM)-containing nanoparticle and compositions comprising such nanoparticles. The nanoparticles can be made using a layer-by-layer deposition method. The nanoparticles can be used in imaging methods such as, for example, cellular imaging methods.