Oxygen Quantification via Probe Lifetime Detection
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Solution Overview
Problem
Current methods for determining oxygen concentration in living cells and tissues, such as those using PpIX, face imprecision due to variations in probe concentration and excitation intensity, leading to inconsistent results.
Innovation Solution
A method that involves exciting a heme precursor like PpIX with optimized light, measuring the temporal evolution of its triplet state, and correlating this with oxygen concentration, considering second-order triplet interactions to improve precision.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional methods using PpIX are used to determine oxygen concentration, then the measurement can be performed in living cells and tissues, but the results are imprecise due to variations in probe concentration and excitation intensity
Solution Approach 1:
The patent changes the measurement parameter from intensity-based to lifetime-based detection. By measuring the lifetime of the triplet state (τ) rather than the intensity of luminescence, the method becomes independent of probe concentration and excitation intensity variations. The Stern-Volmer relationship is applied to correlate lifetime changes with oxygen concentration: τ0/τ = 1 + Ksv[O2], where τ0 is the lifetime without oxygen, τ is the lifetime with oxygen, and Ksv is the Stern-Volmer constant.
2Adaptability or versatility
If probe concentration and excitation intensity are not controlled, then the method can be applied in vivo in living tissues, but measurement variability increases
Solution Approach 1:
The patent replaces the mechanical/control-based approach (controlling probe concentration and excitation intensity) with a physics-based approach (measuring lifetime). The lifetime measurement inherently compensates for variations in these parameters, allowing in vivo application without strict control of probe concentration or excitation intensity. This substitution enables versatility while maintaining precision through the fundamental physics of lifetime quenching.
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 provides more accurate and reliable measurements of oxygen concentration by accounting for second-order reactions, reducing variability and enhancing the reliability of tissue oxygenation assessments.
Implementation Method 1
measuring the lifetime of the luminescence, e.g., delayed fluorescence, exhibited by said probe
Implementation Method 2
exhibiting luminescence (delayed fluorescence or phosphorescence) and or transient triplet absorption
Implementation Method 3
wherein, in the presence of the quencher, the lifetime of an excited triplet state is shortened as compared to the lifetime of an excited triplet state in the absence of the quencher
Implementation Method 4
measuring the lifetime of the luminescence... wherein, in the presence of the quencher, the lifetime of an excited triplet state is shortened
Data Source
AI summary
The disclosure relates to methods and devices for monitoring the concentration of a substance, preferably oxygen, in a cell or tissue, e.g., in cells of the human skin. In particular, it provides a method for determining the concentration of a quencher, such as oxygen and/or the concentration of a probe, e.g., a heme precursor such as protoporphyrin IX (PpIX), wherein the probe is capable of exhibiting luminescence (delayed fluorescence (DF) or phosphorescence) and or transient triplet absorption, preferably, deDF, in a living cell. The method comprises steps of exciting the probe, measuring the lifetime of the luminescence exhibited by said probe, herein, in the presence of the quencher, the lifetime is shortened as compared to the lifetime in the absence of the quencher, and correlating said lifetime with said concentration. The disclosed method leads to more precise results than conventional methods, because of adaptations based on the understanding of the influence of the concentration of the probe and its excitation fluence rate (intensity) on the analysis. For example, the simultaneous time-resolved detection of the probe excimer and monomer DF allows estimation of the probe concentration and compensation of the probe self-quenching effect in the quencher concentration calculation, increasing the measurement precision. Taking into account second order triplet interactions also permits the interpretation of non-exponential decays and further improvement of the quencher and probe concentration estimation. Disclosed methods rely, e.g., on measurement at different emission wavelengths and application of an adaptive Stern-Volmer relationship, the decay central fitting method and/or a mixed orders approach. Said method can be applied, e.g., for bedside monitoring of patients. Also disclosed is the use of the PpIX precursor 5-aminolevulinic acid (5-ALA), or derivatives thereof, in this method, and a device suitable therefor.