Tri-color Dual Glucose Oxygen Fluorescence Sensor
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Solution Overview
Problem
Current methods for monitoring glucose metabolism in cells, particularly in cancer cells, lack real-time direct assays and often use nonmetabolizable glucose analogs that induce metabolic stress, failing to provide continuous and accurate measurements.
Innovation Solution
Development of optical fluorescence sensors comprising a probe for sensing glucose, an intra-reference probe, and a matrix, which allow for ratiometric determination of glucose concentration using a dual sensor system that includes a probe for sensing oxygen, enabling simultaneous monitoring of glucose and oxygen levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If nonmetabolizable glucose analogs are used for detection, then glucose metabolism can be monitored, but metabolic stress is induced in cells leading to cell death
Solution Approach 1:
The patent uses an intermediary fluorescent probe system that indirectly detects glucose metabolism through metabolic byproducts or associated cellular processes, rather than directly using glucose analogs. This intermediary approach allows measurement of glucose metabolism while avoiding the harmful metabolic stress caused by nonmetabolizable analogs.
Solution Approach 2:
The patent replaces the chemical/metabolic detection mechanism (using glucose analogs that interfere with cellular metabolism) with an optical detection mechanism (fluorescence sensing). This substitution eliminates the need for cells to metabolize the probe, thereby avoiding metabolic stress while still enabling real-time monitoring of glucose metabolism.
2Measurement precision
If traditional assay techniques are used, then glucose metabolism can be measured, but real-time continuous monitoring is not achieved
Solution Approach 1:
The patent implements continuous fluorescence monitoring that provides real-time tracking of glucose metabolism dynamics. The fluorescent probes remain active in living cells, enabling uninterrupted observation of metabolic processes over time, unlike traditional endpoint assays that require cell lysis and provide only snapshot measurements.
Solution Approach 2:
The patent utilizes changes in fluorescence parameters (intensity, wavelength, lifetime) in response to glucose metabolism-related changes in the cellular environment. This allows real-time detection of metabolic activity through optical parameter changes without requiring physical sampling or disruption of cells.
3Device complexity
If single-color fluorescence sensors are used, then device complexity is reduced, but measurement accuracy and reliability are compromised
Solution Approach 1:
The patent employs multi-color fluorescence sensing where different fluorescent probes with distinct emission wavelengths are used to detect different aspects of glucose metabolism or to provide internal references. Each color channel provides specific local information, and their combination enhances overall measurement reliability through ratiometric or multi-parameter analysis.
Solution Approach 2:
The patent uses composite fluorescent probe systems combining multiple fluorophores with different spectral properties within a single sensing platform. This composite approach enables simultaneous detection of multiple parameters or provides internal calibration references, improving measurement accuracy while maintaining a unified sensor structure.
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
The sensors provide a robust, reversible, and stable means to accurately monitor glucose and oxygen concentrations in real-time, suitable for biological environments, overcoming the limitations of existing methods by offering continuous and stress-free glucose metabolism assessment.
Implementation Method 1
Shinkai and his colleagues developed organic boronic acids by a modification of anthracene with a bis-phenylboronic acid (GS-COOH, FIG. 1) and its derivatives, which possess photo-induced electron transfer (PET) effect
Implementation Method 2
optical fluorescence dual sensor comprising a probe for sensing glucose, a probe for sensing oxygen
Data Source
AI summary
The present disclosure relates to an optical fluorescence sensor comprising a probe for sensing glucose, an intra-reference probe, and a matrix. The present disclosure also relates to an optical fluorescence dual sensor comprising a probe for sensing glucose having two boronic acid moieties, a probe for sensing oxygen comprising modified porphyrin, an intra-reference probe that is rhodamine-based, and a matrix. The present disclosure additionally relates to methods of preparing these sensors and methods of using them.