Assay Range Extension via Dynamic Calibration Curve Selection
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Solution Overview
Problem
Current calibration curves in clinical diagnostic analyzers often limit the measuring range due to non-linearity and saturation effects, leading to inaccurate analyte concentration measurements, especially at low and high concentrations, and require additional experiments to extend the range.
Innovation Solution
Generating multiple dose-response curves from a single reaction by selecting measurement time windows, allowing for the combination of these curves to expand the measuring range without the need for additional reactions, and using decision rules to select the appropriate calibration curve based on signal strength.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of time
If a single calibration curve is used for measurement, then the measurement process is simple and quick, but the measuring range is limited due to non-linearity and saturation effects
Solution Approach 1:
The system dynamically selects between multiple calibration curves based on the measured signal strength. The analyzer first performs a measurement using a primary calibration curve, and if the signal falls outside the acceptable range (indicating saturation or non-linearity), it automatically selects a secondary calibration curve and performs another measurement. This dynamic adaptation allows the system to maintain both speed and extended measuring range.
Solution Approach 2:
The invention changes the parameter of calibration curve selection based on signal strength. By having multiple calibration curves with different characteristics (some optimized for linear ranges, others for saturation-prone ranges), the system can select the appropriate curve parameter set based on the observed signal, thereby extending the overall measuring range while maintaining measurement simplicity.
2Adaptability or versatility
If the measurement time window is extended to cover broader ranges, then the measuring range increases, but the measurement precision decreases due to saturation and non-linearity
Solution Approach 1:
The invention segments the measuring range into multiple zones, each covered by a different calibration curve. Instead of using one calibration curve for the entire range, the system divides the measurement space and assigns specific calibration curves to specific signal strength ranges. This segmentation ensures that each segment maintains high precision while the combination of segments provides extended overall coverage.
Solution Approach 2:
The system uses feedback from the initial measurement signal strength to determine which calibration curve to use. If the signal indicates saturation or non-linearity, the system feedbacks to select a different calibration curve and performs another measurement. This feedback mechanism ensures that the most appropriate calibration curve is used for each measurement, maintaining precision across the extended range.
3Adaptability or versatility
If multiple calibration curves are used to extend the measuring range, then the measuring range increases, but the device complexity and processing time increase
Solution Approach 1:
The system performs self-service by automatically selecting the appropriate calibration curve based on the measured signal strength. The software includes decision logic that autonomously determines which calibration curve to use without requiring manual intervention or complex configuration. This self-service approach minimizes the operational complexity despite having multiple calibration curves available.
Solution Approach 2:
The system uses dynamic selection of calibration curves based on real-time signal assessment. Rather than requiring complex pre-programming for every possible scenario, the system dynamically adapts by selecting from available calibration curves based on the observed signal characteristics. This dynamic approach simplifies the overall system architecture compared to static, overly-complex solutions.
4Measurement precision
If a short time window with tight tolerances is used for measurement, then the measurement precision is high, but the measuring range is limited
Solution Approach 1:
The invention segments the measurement process into multiple stages, each using appropriate time windows and calibration curves. The first measurement uses a standard time window with a primary calibration curve for high precision in the normal range. If the signal indicates the need for extended range measurement, a second measurement is performed with adjusted parameters. This segmentation allows each stage to optimize for its specific purpose while the combination provides both precision and extended range.
Solution Approach 2:
The system dynamically adjusts the measurement time window and calibration curve selection based on the initial signal assessment. Rather than using a fixed time window for all measurements, the system adapts the measurement parameters dynamically, selecting longer or shorter time windows and appropriate calibration curves based on the observed signal strength and characteristics, thereby achieving both precision and extended range.
Data Source
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AI summary
Disclosed is a use of reaction kinetics to generate multiple dose-response curves from a single reaction, thus eliminating the need to run a second experiment with additional sample, reagents, and time to cover a broader measuring range than is available in a standard assay. Using a single protocol, the differences in the reaction kinetics for different sample concentrations yield different responses at different measurement times. Selection of the appropriate dose-response curve cross-section increases the measuring range and accuracy of the assay from a single reaction without substantially increasing imprecision. Several overlapping dose-response curves are pieced together to provide a standard curve to ensure continuity throughout the expanded measuring range.