Assay Dynamic Range Extension via Digital-Analog Signal Segmentation
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Solution Overview
Problem
Current analytical methods are limited by their dynamic range, struggling to accurately detect and quantify analyte molecules or particles at low concentrations, and often lack the sensitivity to effectively measure molecules or particles present at very low concentrations.
Innovation Solution
The system combines digital and analog detection methods, using a substrate with immobilized analyte molecules or particles and a detector to produce signals varying with concentration, allowing for both digital counting at low concentrations and intensity-based analysis at higher concentrations, with a calibration curve linking both methods for extended dynamic range.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional analytical methods are used, then the methods can detect analyte molecules at moderate concentrations, but they fail to accurately detect and quantify analyte molecules at very low concentrations due to limited dynamic range and sensitivity
Solution Approach 1:
The patent divides the detection process into two distinct modes: digital mode for low concentrations (detecting individual molecules) and analog mode for high concentrations (measuring aggregate signal intensity). This segmentation allows the system to optimize detection accuracy for each concentration range separately, resolving the contradiction between measurement precision and quantity of substance detection.
2Adaptability or versatility
If a single detection method is used, then the system is simple to operate, but it cannot extend the dynamic range beyond traditional limits
Solution Approach 1:
The patent creates a universal detection system that can operate in both digital and analog modes using the same physical platform (detector, substrate, and signal processing infrastructure). This multi-functionality allows the system to adapt to different concentration ranges without requiring separate detection systems, thus extending dynamic range while controlling complexity.
Solution Approach 2:
The system dynamically switches between digital and analog detection modes based on the concentration of analyte molecules. At low concentrations, it operates in digital mode with high sensitivity; at high concentrations, it transitions to analog mode. This dynamic adaptability extends the usable dynamic range while maintaining a relatively simple underlying system architecture.
3Measurement precision
If digital counting method is used, then sensitivity is improved for low concentrations, but the method cannot accurately measure higher concentrations
Solution Approach 1:
The detection system dynamically adapts its measurement approach based on analyte concentration. In digital mode, it counts individual molecules for high sensitivity at low concentrations. When concentration increases, the system transitions to analog mode where it measures aggregate signal intensity, allowing accurate measurement across the full concentration range from femtomolar to micromolar levels.
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 enables accurate measurement of analyte concentrations over a wide range, from very low femtomolar to high micromolar levels, with improved sensitivity and precision, extending the dynamic range beyond traditional methods.
Implementation Method 1
at least one detector configured to address a plurality of the locations, able to produce at least one signal indicative of the presence or absence of an analyte molecule or particle at each location addressed and having an intensity varying with the number of analyte molecules or particles at each location
Data Source
AI summary
Described herein are systems and methods for extending the dynamic range of assay methods and systems used for determining the concentration of analyte molecules or particles in a fluid sample. In some embodiments, a method comprises spatially segregating a plurality of analyte molecules in a fluid sample into a plurality of locations. At least a portion of the locations may be addressed to determine the percentage of said locations containing at least one analyte molecule. Based at least in part on the percentage, a measure of the concentration of analyte molecules in the fluid sample may be determined using an analog, intensity-based detection/analysis method/system and/or a digital detection/analysis method/system. In some cases, the assay may comprise the use of a plurality of capture objects.