Biosensing System for Low-Concentration Analyte Monitoring
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Solution Overview
Problem
Current technologies face challenges in rapidly monitoring low-concentration analytes over long time spans while maintaining sensitivity and short time delays.
Innovation Solution
A biosensing system utilizing high-affinity binder molecules in a limited-volume assay with a reversible detection principle and time-controlled sampling, allowing for optimal tradeoffs between time characteristics and sensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If high-affinity binder molecules with low dissociation rate constants are used, then sensitivity for low-concentration analytes is improved, but time delay and incubation time increase
Solution Approach 1:
The patent implements periodic sampling and measurement cycles, where the analyte concentration is measured at multiple time points within each cycle. This allows the system to capture dynamic changes while using the high-affinity binders, as the periodic measurement approach extracts sufficient information without requiring continuous equilibrium states, thereby reducing overall time delay while maintaining sensitivity.
Solution Approach 2:
The patent employs a limited-volume assay where the measurement chamber contains a limited number of binding sites that are in excess relative to the analyte concentration. This partial saturation approach allows the system to achieve detectable signal changes with high-affinity binders without requiring complete equilibrium, thus reducing incubation time while preserving the sensitivity benefits of low dissociation rate constants.
2Measurement precision
If high-affinity binder molecules with low dissociation rate constants are used, then sensitivity for low-concentration analytes is improved, but time interval between successive measurements increases
Solution Approach 1:
The system performs multiple measurements within each sampling cycle at different time points, enabling frequent monitoring without requiring the binder to reach full equilibrium each time. The periodic structure allows rapid successive measurements by utilizing the binding kinetics during the cycle rather than waiting for complete equilibrium, thus increasing measurement frequency while maintaining high sensitivity through the use of low koff values.
Solution Approach 2:
The measurement chamber is pre-equilibrated with the binder molecules before each sampling event. This preliminary preparation ensures that the binders are ready to immediately interact with incoming analyte, eliminating the need for lengthy equilibrium establishment periods between successive measurements, thereby increasing productivity while preserving sensitivity.
3Measurement precision
If reagents are consumed for every sample taken, then measurement sensitivity is maintained, but long-term monitoring becomes complicated and resource-intensive
Solution Approach 1:
The measurement chamber contains a limited number of binding sites that are regenerated after each measurement cycle through the dissociation of analyte-binder complexes. The system uses the natural reversibility of the binding interaction to restore available binding sites without requiring additional reagents, enabling long-term monitoring with minimal reagent consumption while maintaining measurement sensitivity through the high-affinity interactors.
Solution Approach 2:
The patent implements a system where analyte-binder complexes that have completed their measurement function are allowed to dissociate, recovering the binder molecules for subsequent measurement cycles. This recovery process eliminates the need to discard or replace reagents after each use, reducing reagent consumption over time while maintaining the sensitivity provided by the high-affinity binders.
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 precise and accurate quantification of low analyte concentrations with significantly shorter time delays and intervals, and allows for continuous monitoring over an endless time span.
Implementation Method 1
The binding sites have a binding affinity to the analyte of interest... The specificity originates from molecular interactions such as charge, hydrogen bonding, van der Waals forces, and hydrophobic and steric effects
Implementation Method 2
facilitating a time-dependent exchange of analyte between the system of interest and the effective volume (Vch) of the measurement chamber
Implementation Method 3
The time-dependent sampling of the analyte of interest may be effectuated by time-dependent exchange of analyte by diffusion, advection, or by another active or passive physicochemical analyte transport method
Data Source
AI summary
A method and biosensing system for monitoring an analyte by measuring the concentration of the analyte in a measurement chamber including an effective number of binding sites having a binding affinity to the analyte, wherein the measurement chamber has an effective volume in which the analyte has a significant probability to encounter the binding sites, and method includes providing a time-dependent sampling of the analyte, by providing a time-dependent exchange of analyte between a system and the effective volume of the measurement chamber, by performing at least one exchange modulation cycle including the steps: a) facilitating a primary exchange phase having a characteristic time of primary exchange and a duration of primary exchange, b) facilitating a primary-to-secondary switching phase having a characteristic primary-to-secondary switching time and a primary-to-secondary switching duration, and c) facilitating a secondary exchange phase having a characteristic time of secondary exchange and a duration of secondary exchange.