Reversible Nanoparticle Aggregates for Protease Detection in Biological Fluids
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Solution Overview
Problem
Existing nanoparticle-based sensors for protease detection suffer from irreversible aggregation in complex biological matrices, leading to false positives and inability to operate effectively in biological fluids.
Innovation Solution
Development of reversible nanoparticle aggregates stabilized with Argx citrate or Kx-Rx citrate-stabilized nanoparticles, conjugated with Z-PEGx peptides that dissociate upon protease cleavage, allowing for monodisperse nanoparticles and colorimetric detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If nanoparticles aggregate to cause color change for protease detection, then detection sensitivity is improved, but the aggregation becomes irreversible leading to false positives and inability to operate in complex biological matrices
Solution Approach 1:
The patent applies dynamics by making the nanoparticle aggregation reversible through pH-responsive behavior. Nanoparticles aggregate at neutral pH for detection but can be redispersed by adjusting pH, allowing multiple measurements and eliminating false positives from irreversible aggregation. This dynamic control enables reliable operation in complex biological matrices.
Solution Approach 2:
The patent utilizes parameter changes by modifying pH conditions to control nanoparticle aggregation state. At pH 7.4, nanoparticles remain aggregated for sensitive detection, while lowering pH to 3-5 causes redispersion for resetting the system. This parameter-based control allows the system to function reliably in complex biological samples without permanent aggregation.
2Illumination intensity
If nanoparticles aggregate in complex biological matrices, then colorimetric signal is enhanced, but false positives occur and the system cannot operate effectively in biological fluids
Solution Approach 1:
The pH-responsive dynamic aggregation allows the system to maintain strong colorimetric signals in complex matrices by controlling aggregation state through pH adjustments, while preventing false positives through reversible redispersion at low pH.
Solution Approach 2:
The patent applies preliminary action by pre-adjusting pH conditions before sample analysis to ensure optimal aggregation state, and using pH adjustment as a preliminary step to eliminate matrix effects before detection, thereby preventing false positives.
3Device complexity
If irreversible aggregation is used for color change detection, then simple detection mechanism is achieved, but the system lacks ability to reset and perform multiple measurements
Solution Approach 1:
The pH-responsive reversible aggregation provides a simple yet effective mechanism for resetting the detection system. By adjusting pH, the same nanoparticle system can be reset for multiple measurements without complex regeneration procedures, significantly improving productivity while maintaining mechanism simplicity.
Solution Approach 2:
The patent applies discarding and recovering by using pH adjustment to recover nanoparticle dispersion from aggregated state, allowing the system to be reset and reused for multiple measurements. This simple chemical recovery method eliminates the need for complex system replacement or regeneration.
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 reliable protease detection in undiluted biological fluids with minimal interference from matrix effects, providing accurate and reversible colorimetric responses.
Implementation Method 1
Plasmonic nanoparticles are colloidally stable when the repulsive electrostatic and steric forces are balanced by the attractive Van der Waals forces
Implementation Method 2
Plasmonic nanoparticles are colloidally stable when the repulsive electrostatic and steric forces are balanced by the attractive Van der Waals forces
Implementation Method 3
This aggregation leads to plasmonic coupling, which in turn leads to a color change
Implementation Method 4
This aggregation leads to plasmonic coupling, which in turn leads to a color change
Implementation Method 5
detecting the presence of a protease in a fluid
Data Source
AI summary
In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for detecting proteases including detecting proteases in a biological sample. In alternative embodiments, products of manufacture, formulations, mixtures or kits are used for stabilizing (or substantially stabilizing) nanoparticles in a reversible aggregate, and, detecting the presence of a protease in a fluid, wherein optionally the products formulations or mixtures can aggregate or assemble into nanoparticles such that the nanoparticles undergo plasmonic coupling, and the plasmonic coupling is reversible (or substantially reversible) leading to monodisperse nanoparticles when a chemical cue or signal is added.