Longitudinal Assay Binding Curve Analysis for Biomarker Detection
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Solution Overview
Problem
Existing detection methods for macro and small molecules, including bio-molecules, often sacrifice sensitivity, speed, or the ability to distinguish specific from non-specific binding, leading to inaccurate biomarker detection and higher false positive rates in clinical and research settings.
Innovation Solution
A method involving a fluid sample passed through a cartridge with a capture agent-coated assay surface, where multiple detections are taken to create a binding curve, allowing for the differentiation of specific and non-specific binding by analyzing the binding curve's shape and rate constants, enabling accurate determination of analyte concentration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If a single detection time point is used in known assay methods, then the assay speed is improved, but the ability to distinguish specific binding from non-specific binding deteriorates
Solution Approach 1:
The patent applies dynamics by transitioning from a static single-time-point detection to a dynamic multi-time-point detection approach. The system continuously monitors binding over time, allowing differentiation between specific binding (which increases over time) and non-specific binding (which remains relatively constant), thereby resolving the contradiction between speed and measurement precision.
Solution Approach 2:
The patent uses preliminary action by performing multiple detections at different time points before final quantification. This preliminary temporal sampling allows the system to establish binding kinetics patterns that distinguish specific from non-specific binding, enabling accurate measurement without requiring extended observation periods for all analytes.
2Measurement precision
If the detection time is optimized for one analyte in a multiplexed assay, then the binding kinetics accuracy for that analyte is improved, but the detection accuracy for other analytes with different binding kinetics deteriorates
Solution Approach 1:
The patent applies universality by creating a detection system that serves multiple functions simultaneously. The multi-time-point detection approach works universally for all analytes regardless of their specific binding kinetics, allowing the same system to accurately measure both fast-binding and slow-binding analytes without requiring analyte-specific optimization.
Solution Approach 2:
The system uses dynamics to adapt to different analyte kinetics automatically. By capturing binding trajectories over time rather than at a fixed time point, the system dynamically adjusts to the binding rate of each analyte, enabling accurate measurement across diverse analytes with varying binding characteristics.
3Measurement precision
If sensitivity is increased to detect low concentration analytes, then the detection limit is improved, but the assay time required to obtain a result increases
Solution Approach 1:
The patent applies preliminary action by performing rapid initial detections to establish the binding trajectory early in the assay. This allows the system to predict final binding levels without requiring the full equilibrium time, thereby achieving sensitive detection of low-concentration analytes in reduced time.
Solution Approach 2:
The system uses skipping by rushing through the early binding phase with multiple rapid detections to capture the binding kinetics quickly. By analyzing the trajectory during this rushed early phase, the system can extrapolate final binding levels without waiting for complete equilibrium, reducing overall assay time while maintaining sensitivity.
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 enhances the sensitivity and accuracy of biomarker detection by isolating specific binding from non-specific binding, reducing false positives and improving the quantification of biomarker concentrations, thus aiding in biomarker discovery and clinical diagnostics.
Implementation Method 1
an assay surface containing a plurality of capture agents for the analyte
Implementation Method 2
non-specific binding of non-analyte components of a tested sample
Implementation Method 3
a detection label (e.g., a fluorescent label)
Data Source
Figure 1A~1C
Figure 2
Figure 3
AI summary
Embodiments of the invention relate generally to macro and small molecule detection and, more particularly, to methods for detecting macro and small molecules, including bio-molecules, in a liquid or gaseous sample. Methods according to embodiments of the invention are useful in the identification, discovery, and validation of biomarkers, as well as the screening of individuals for such biomarkers for diagnostic, therapeutic, and forensic purposes. In one embodiment, the invention provides a method of detecting an analyte in a fluid sample, the method comprising: passing a fluid sample containing a labeled analyte across at least one assay surface containing a capture agent for the analyte; detecting the labeled analyte; repeating the passing and detecting steps at least once; and creating a binding curve for the analyte based on the detecting of the labeled analyte.