Biased Hinge Molecular Sensor for Dynamic Analyte Tracking
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current molecular sensors face challenges in achieving sensitive and dynamic tracking of analyte concentrations due to the ligand binding domain and sensor domain remaining in the ON state for extended periods, leading to interference with endogenous systems and difficulty in monitoring fine-scale temporal and spatial changes.
Innovation Solution
A sensor molecule with a biased hinge mechanism, allowing frequent transitions between bound and unbound conformations, featuring a rod-like structure connected by a joint molecule with target binding and binding molecules arranged to bind to the same epitope or nucleic acid sequence, enabling dynamic switching between ON and OFF states.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If the ligand binding domain and sensor domain are kept in the ON state for extended periods to maintain a strong signal, then the signal-to-noise ratio is improved, but the sensor interferes with endogenous systems and cannot track fine-scale temporal and spatial changes
Solution Approach 1:
The patent applies the dynamics principle by designing a sensor with a biased hinge that enables frequent transitions between bound and unbound conformations. This dynamic switching allows the sensor to maintain a strong average signal while minimizing prolonged interference with endogenous systems, resolving the contradiction between signal strength and biological compatibility
2Measurement precision
If the sensor remains in the ON state for extended periods to ensure detectable signal, then the measurement sensitivity is improved, but the latency in detecting analyte concentration changes increases
Solution Approach 1:
The patent implements periodic action through the biased hinge mechanism that causes the sensor to oscillate between bound and unbound states. This periodic switching enables the sensor to rapidly respond to changes in analyte concentration, reducing detection latency while maintaining sufficient signal intensity through the cumulative effect of repeated binding events
3Measurement precision
If the sensor protein is made larger to enhance binding affinity and signal strength, then the measurement precision is improved, but the ability to penetrate cellular barriers is reduced
Solution Approach 1:
The patent applies parameter changes by optimizing the hinge bias and conformational transition kinetics rather than simply increasing protein size. This allows the sensor to achieve high binding affinity and strong signal through enhanced binding kinetics and efficient conformational switching, while maintaining a compact size that enables penetration of cellular barriers
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 design allows for rapid dissociation from targets when concentrations drop, enabling faster tracking of changes, smaller protein-based sensors that can penetrate cellular barriers, and reduced latency in detecting analyte concentrations, while maintaining a strong signal-to-noise ratio.
Implementation Method 1
The invention relates to molecular sensors, such as unimolecular sensors, and methods using intramolecular resonance energy transfer (RET) and fluorescence for detecting the presence of analytes or ligand binding
Data Source
AI summary
The invention relates to a sensor molecule for detecting a target molecule comprising: (a) a rod-like molecule L and a rod-like molecule R connected to each other by a joint molecule C to form a hinge; (b) a target binding molecule A bonded to the end of rod-like molecule L opposite to the joint molecule C; (c) a binding molecule A′ bonded to the end of rod-like molecule R opposite the joint molecule C; wherein the target binding molecule A is arranged to bind to an epitope or nucleic acid sequence of the target molecule to be detected, and binding molecule A′ is arranged to bind to the same epitope or same nucleic acid sequence, or portion thereof of the target molecule as target binding molecule A; and wherein the hinge is biased into an open position, such that target binding molecule A and binding molecule A′ are biased apart by the hinge. The invention also relates to analyte dependent activation of pharmaceuticals and chemo-toxins.