Ratiometric Fluorescence Sensor Diagnostics

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Solution Overview

Problem

Existing continuous glucose sensors face challenges in diagnosing performance due to noisy intensity signals, making it difficult to distinguish analyte concentration changes from system disturbances without measuring the isosbestic point, which complicates sensor diagnostics and requires additional measurements.

Innovation Solution

A method and system using matrix-suspended glucose binding protein labeled with an environmentally sensitive dye that measures fluorescence intensities at frequencies higher and lower than the isosbestic frequency to derive a glucose-independent intensity coefficient (GIIC) for determining sensor performance, allowing for analyte-independent diagnostics without additional measurements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If intensity signals are used for glucose measurement, then the sensor can detect analyte concentration, but the signals are inherently noisy and difficult to distinguish from system disturbances

Engineering Contradiction:

Improveglucose concentration measurement accuracyVSAvoidnoise in intensity signals

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent transforms the measurement approach by changing from direct intensity measurement to ratiometric measurement. By measuring intensity at multiple wavelengths and forming ratios, the system converts noisy absolute intensity signals into stable relative signals that are insensitive to system disturbances while retaining analyte concentration information.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces an intermediary reference wavelength (isosbestic point) that does not respond to analyte concentration changes but does respond to system disturbances. This reference serves as a mediator to distinguish between analyte-related signal changes and system-related noise, enabling accurate glucose measurement despite noisy intensity signals.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If the isosbestic point is measured to diagnose sensor performance, then system disturbances can be detected, but additional measurements are required which complicates the system

Engineering Contradiction:

Improvesensor performance diagnosis capabilityVSAvoidnumber of measurement wavelengths

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent makes the measurement system universal by selecting wavelength pairs that simultaneously provide both analyte concentration information and system performance diagnostic capability. The same two wavelengths used for glucose measurement also enable detection of sensor degradation and system disturbances through the derived intensity coefficient, eliminating the need for separate diagnostic measurements.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent merges the analyte measurement function and the diagnostic function into a single measurement process. By carefully selecting the two measurement wavelengths and processing their intensities together, the system extracts both glucose concentration and system health information from the same signal pair, reducing overall system complexity.

Inventive Principle:

Principle #5Merging (Combining)

3Measurement precision

If ratiometric sensing is used to reduce noise, then measurement accuracy improves, but both measured frequency bands change in response to analyte concentration and system changes making diagnosis difficult

Engineering Contradiction:

Improvesignal stabilityVSAvoidsensor performance diagnosis

Core Design Contradiction:

Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent segments the signal information by deriving separate parameters from the two wavelength measurements: one parameter (ratio) captures analyte concentration information while the other (intensity coefficient) captures system performance information. This segmentation allows independent analysis of analyte measurement quality and sensor health status despite both wavelengths being affected by different factors.

Inventive Principle:

Principle #1Segmentation

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 robust analyte measurement and sensor diagnostics using the same signal pair, minimizing system complexity and providing a stable, noise-free signal for monitoring sensor performance, effectively separating analyte concentration changes from system changes.

Implementation Method 1

The dye fluoresces at an intensity related to a concentration of the analyte concentration in the environment

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Implementation Method 2

Ratiometric sensing takes advantage of a very stable property of dye emission spectra. That is, the ratio of different bands within the spectra is relatively insensitive to changes in the overall intensity of the spectra

Methodology Applied

Scientific EffectRatiometric sensing:

Data Source

PatentUS10466247B2System and method for diagnosing sensor performance using analyte-independent ratiometric signals

Publication Date: 2019.11.05 BECTON DICKINSON & CO

AI summary

A system and method are provided for utilizing radiometric fluorescence detection to determine a glucose independent concentration value when measuring frequency bands that do not contain the system isosbestic point. Preferably two bands are chosen such that a first band is below the system isosbestic point, and a second band is above the system isosbestic point, and both points are sufficiently far from the frequency endpoints to maximize the signal to noise ratio.