LSPR Microscopy Chip for Quantitative Binding Kinetics Mapping
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Solution Overview
Problem
Current localized surface plasmon resonance (LSPR) biosensing technologies lack methods for quantitative determination of surface receptor occupancy and spatial-temporal mapping on a commercially available light microscopy platform, limiting their effectiveness compared to mature surface plasmon resonance (SPR) techniques.
Innovation Solution
A chip with patterned plasmonic nanostructures on a glass coverslip for LSPR biosensing, enabling real-time fractional occupancy measurements and spatio-temporal mapping using electron beam nanolithography, compatible with standard microscopes, and integrated with fluorescence and differential interference contrast microscopy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If LSPR biosensing is implemented on commercially-available light microscopy platforms, then ease of operation and accessibility are improved, but quantitative determination of surface receptor occupancy and spatiotemporal mapping capabilities are lacking
Solution Approach 1:
The patent transforms LSPR from a qualitative optical phenomenon into a quantitative measurement tool by establishing mathematical relationships between LSPR signal changes and surface receptor occupancy parameters. This enables precise quantification while maintaining compatibility with standard light microscopy platforms.
Solution Approach 2:
The patent replaces complex custom-built SPR instrumentation with commercially-available light microscopy systems by substituting the detection mechanism. Instead of using specialized SPR detectors, the invention uses standard microscope cameras and detectors to capture LSPR signals, achieving quantitative biosensing through optical parameter analysis.
2Manufacturing precision
If LSPR imaging is performed with high spatial resolution, then spatial mapping of binding events is improved, but temporal resolution and real-time monitoring capabilities are limited
Solution Approach 1:
The patent divides the imaging field into discrete spatial regions and implements time-resolved LSPR measurements across multiple segments. By segmenting both space and time, the system achieves high spatial resolution mapping while capturing temporal dynamics through sequential measurements at different locations.
Solution Approach 2:
The patent implements dynamic, real-time LSPR imaging by continuously monitoring temporal changes in LSPR signals across spatially-resolved regions. The system captures time-dependent variations in receptor occupancy and binding events, enabling simultaneous high spatial and temporal resolution through dynamic measurement protocols.
3Adaptability or versatility
If LSPR biosensing integrates with traditional microscopy techniques like fluorescence and DIC, then versatility and adaptability are improved, but system complexity and calibration requirements increase
Solution Approach 1:
The patent creates a universal LSPR detection platform that functions across multiple microscopy modalities including fluorescence, DIC, and brightfield imaging. By designing the LSPR assay to be modality-agnostic, the system achieves multi-functionality without requiring separate calibration protocols for each imaging technique.
Solution Approach 2:
The patent implements self-calibrating LSPR measurements that automatically reference internal standards or control regions within the field of view. This self-service approach eliminates complex external calibration procedures, allowing seamless integration with traditional microscopy techniques while maintaining measurement accuracy.
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 real-time, quantitative determination of surface receptor occupancy and spatio-temporal mapping of binding events with high spatial and temporal resolution, integrating with traditional imaging techniques on a standard microscope platform.
Implementation Method 1
Localized surface plasmon resonance (LSPR) is an emerging technique in the field of label-free biosensing which is currently dominated by the closely related, but more mature surface plasmon resonance (SPR) technique. Both employ the coupling of light with metallic structures for the excitation of a plasmonic resonance and both take advantage of the fact that the resonance is sensitive to changes in the index of refraction near the metallic surface
Implementation Method 2
In SPR, total internally reflected light, typically introduced by a prism, is incident at the 'resonant' angle that excites surface plasmon polaritons propagating laterally along a planar, thin metal film
Data Source
AI summary
A method for the spatiotemporal mapping of receptor-ligand binding kinetics in localized surface plasmon resonance (LSPR) imaging using a chip for LSPR imaging having a glass coverslip compatible for use in a standard microscope and at least one array of functionalized plasmonic nanostructures patterned onto the glass coverslip with electron beam nanolithography and projecting a magnified image of the array to a CCD camera and monitoring the binding kinetics of the array. The nanostructures can be regenerated allowing the chip to be used multiple times.