Hyperpolarized Xenon NMR for Host-Molecule Quantification
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Solution Overview
Problem
Existing methods for determining host molecule concentration using hyperpolarized xenon are limited by high uncertainty, require extensive prior knowledge, and are difficult to implement without reference materials, especially in biological samples.
Innovation Solution
A method and device that calculate host molecule concentration using signal intensities, xenon concentrations, and irradiation parameters, eliminating the need for reference materials by measuring xenon solubility and partial pressure, and applying Henry's law to determine host molecule concentration through fitting and minimization of error.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If HyperCEST techniques are used to determine host molecule concentration, then sensitivity is improved, but measurement precision deteriorates due to high uncertainty and difficulty in quantification
Solution Approach 1:
The patent introduces xenon as an intermediary substance that binds to the host molecule and serves as a reporter for NMR detection. By measuring the xenon signal instead of directly detecting the host molecule, the method achieves reliable quantification with reduced uncertainty, as xenon provides a strong, detectable signal that correlates with host molecule concentration
Solution Approach 2:
The patent utilizes changes in NMR signal parameters (frequency, intensity, relaxation times) of xenon based on its binding state to the host molecule. By analyzing these parameter changes, particularly the chemical shift and signal intensity variations between free and bound xenon, the method achieves both high sensitivity and reliable concentration determination
2Measurement precision
If reference materials are used for calibration, then measurement precision improves, but device complexity and ease of operation worsen due to extensive preparation and prior knowledge requirements
Solution Approach 1:
The method enables self-calibration by using the xenon signal itself as the reference. The known properties of xenon (its NMR characteristics and binding behavior) allow the system to determine host molecule concentration without requiring external reference materials or complex calibration procedures, thereby reducing device complexity while maintaining measurement precision
Solution Approach 2:
Xenon serves multiple functions simultaneously: it acts as both the probe molecule for detecting host molecule presence and as an internal reference for quantification. This multi-functionality eliminates the need for separate reference materials and simplifies the overall measurement process while maintaining accuracy
3Ease of operation
If host molecule concentration is determined using conventional NMR, then ease of operation is maintained, but measurement precision deteriorates due to inability to detect low concentrations
Solution Approach 1:
The patent exploits changes in NMR parameters of xenon upon binding to the host molecule, particularly the chemical shift and signal intensity. These parameter changes provide a sensitive indicator of host molecule concentration that can be detected using conventional NMR equipment, maintaining ease of operation while dramatically improving measurement precision and detection sensitivity
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
Enables accurate determination of host molecule concentrations with low uncertainty, allowing for quantitative research, especially in biological samples, with measurement uncertainties below 20% and sensitivity to detect concentrations as low as one nanomole per liter.
Implementation Method 1
A further increase in sensitivity is achieved by the use of NMR saturation transfer techniques—provided according to a preferred embodiment—in which the presence of the host molecule is indirectly observed (hyperpolarized xenon chemical exchange saturation transfer, HyperCEST)
Implementation Method 2
The invention relates to a method for quantitatively determining a host molecule concentration Ctot of host molecules in a solution 16 using magnetic resonance and, more particularly, using 129Xe NMR
Implementation Method 3
Specifically, it is determined as the product of the xenon solubility (s) of xenon in the solution and the xenon partial pressure (p) in a gas in exchange equilibrium with the solution, according to Henry's law
Data Source
Figure 1a~1d
Figure 2
Figure 3a(a)~3b(c)
AI summary
The invention relates to a method for quantitatively determining a host-molecule concentration (Ctot) of host molecules (10), comprising the steps of: (a) introducing hyperpolarized xenon into a solution (16) of host molecules (10) so that a xenon-containing solution (16) is produced, which contains dissolved xenon and xenon in a host-molecule–xenon complex (14) with a host molecule (10), (b) irradiating the xenon-containing solution (16) with depolarizing electromagnetic radiation (18) having a host-complex frequency (fw) in order to at least partially selectively depolarize xenon in the host-molecule–xenon complex (14), and (c) thereafter, measuring a signal intensity (S) of a high-frequency signal (20) at least in a frequency interval about a resonance frequency (fR) of the dissolved xenon at at least two different times of the irradiation (t). According to the invention, (d) xenon-containing solutions (16) of different xenon concentrations (ρ) of dissolved xenon are irradiated with depolarizing radiation (18) of different irradiation amplitudes (ν) and irradiation times (t), and the respective signal intensities (S(ρ,ν,t)) are detected, and (e) the host-molecule concentration (Ctot) is determined from the signal intensities (S(ρ,ν,t)), xenon concentrations (ρ) of dissolved xenon, irradiation amplitudes (ν) and irradiation times (t).