Optical Sensor Mass Transport Normalization via Electrostatic Binding
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Solution Overview
Problem
Existing label-free analytical sensor systems face challenges in normalizing mass transport properties across different optical sensor surfaces, leading to variations in calibration-free concentration analysis due to differences in flow cell characteristics, which can be difficult to correct without consuming the chip.
Innovation Solution
The method involves electrostatic binding of positively charged macromolecular particles to the carboxydextran surface of optical sensing surfaces at pH below the isoelectric point and low ionic strength, allowing for characterization and normalization of mass transport properties, and subsequent washing with a buffer of higher ionic strength to remove the particles, enabling accurate concentration measurement of analytes without relying on active binding.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If calibration-free concentration analysis is performed using mass transport properties, then concentration can be determined without labeling, but variation among different sensor chips causes significant measurement errors
Solution Approach 1:
The patent changes the charge state parameter of the analyte by adjusting pH to below its isoelectric point, transforming it from neutral/negative to positively charged. This enables electrostatic binding to the negatively charged carboxydextran surface, creating a standardized interaction that is independent of chip-specific variations and enables reliable normalization across different sensor chips
Solution Approach 2:
The patent introduces electrostatic interaction as an intermediary mechanism between the analyte and sensor surface. By using electrostatically bound particles as a mediator, the system normalizes mass transport properties across different chips without requiring active ligand binding, thus resolving chip-to-chip variability while maintaining measurement precision
2Reliability
If correction for chip variation is performed using interactions between immobilized ligand and analyte, then chip differences can be corrected, but the chip is consumed in the process
Solution Approach 1:
The patent enables the sensor surface to normalize itself by exploiting the inherent negative charge of the carboxydextran coating. The surface automatically binds positively charged analytes through electrostatic attraction without requiring external ligands, allowing chip characterization and normalization without consuming the sensor surface
Solution Approach 2:
Instead of immobilizing ligands on the sensor surface to capture analytes, the patent inverts the approach by allowing freely circulating positively charged analytes to bind electrostatically to the naturally negatively charged surface. This reversal enables chip normalization without ligand immobilization, preserving the sensor surface for subsequent measurements
3Reliability
If electrostatic binding is used to normalize mass transport properties, then chip variation is reduced, but the method requires specific pH and ionic strength conditions
Solution Approach 1:
The patent applies preliminary action by adjusting the pH and ionic strength of the buffer before the measurement process. By pre-conditioning the buffer to ensure the analyte is positively charged and the surface is sufficiently negative, the method establishes optimal electrostatic binding conditions that enable reliable mass transport normalization across all subsequent measurements
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 approach reduces variation among different sensor chips, allows for accurate calibration-free concentration analysis, and measures analyte concentration independently of active binding, making it suitable for multi-channel systems by characterizing mass transport properties and correcting for chip-to-chip differences without depleting the sensor surface.
Implementation Method 1
electrostatic binding of positively charged macromolecular particle to the carboxydextran surface of an optical sensing surface
Implementation Method 2
characterize the mass transport properties of a flow cell
Implementation Method 3
The electrostatically bound macromolecular particles are washed away when buffer with physiological ionic strength is flown over the chip
Data Source
AI summary
The invention relates to a method for normalization of a label-free system for calibration-free concentration analysis. The method comprises (1) providing a solution containing a control macromolecular particle of a known concentration at a pH lower than the pI of the macromolecular particle and a low ionic strength; (2) contacting the solution with a negatively charged optical sensor surface at a first flow rate to allow electrostatic binding of the macromolecular particle to the surface and obtaining a first sensorgram; (3) contacting the solution with the optical sensor surface at a second flow rate to allow electrostatic binding of the macromolecular particle to the surface and obtaining a second sensorgram; and (4) fitting the sensorgrams to a binding equation to determine a measured concentration of the control; wherein the optical sensor surface is not immobilized with a ligand for the control and the contacting steps are performed under mass transport limitations. Also provided is a kit for performing the method, as well as a method for determining a concentration of an analyte.