NMR Spectroscopy Selective Crystal Detection
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Solution Overview
Problem
Current NMR measurement techniques fail to selectively acquire information from a crystal of interest within a solid sample without being affected by other crystals or diluent components, which is crucial for analyzing active pharmaceutical ingredients in medical drugs or specific domains in amorphous materials or polymer blends.
Innovation Solution
A method and apparatus that manipulate nuclear spins of particular atoms in the crystal of interest to cause initial magnetization in nearby hydrogen atoms, which is then spread to peripheral hydrogen atoms within the same crystal, allowing for selective observation of magnetization without extending to outside crystals, using sub pulse sequences and magic angle spinning techniques.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional NMR measurement is performed on a solid sample containing multiple crystals, then NMR signals from all crystals are detected, but it becomes impossible to selectively acquire information from a specific crystal of interest without interference from other crystals and diluent components
Solution Approach 1:
The patent applies segmentation by dividing the solid sample into individual crystal particles and selectively manipulating nuclear spins within each crystal. By using particle isolation techniques and localized spin manipulation, the method segments the NMR signal source to focus only on the crystal of interest, excluding signals from other crystals and diluent components.
Solution Approach 2:
The patent implements local quality by applying specific pulse sequences and magnetic field manipulations to targeted regions within the solid sample. The spin manipulation is localized to hydrogen atoms associated with particular crystals, creating spatially selective NMR signals that reflect the chemical environment of specific crystal domains while ignoring surrounding materials.
2Measurement precision
If diluent components are present in the sample to form medical drugs, then the active pharmaceutical ingredient can be delivered, but the diluent components generate unwanted NMR signals that interfere with analysis of the active ingredient
Solution Approach 1:
The patent extracts the NMR signal information specifically from the active pharmaceutical ingredient crystals by selectively manipulating spins associated with those crystals. The method separates the desired signal from the diluent signals through localized spin manipulation and signal processing techniques, effectively extracting only the relevant chemical information while eliminating diluent interference.
Solution Approach 2:
The patent uses hydrogen atoms as an intermediary to transfer and detect spin information from the active ingredient molecules. By focusing spin manipulation on hydrogen atoms associated with the API crystals and using them as mediators for signal detection, the method indirectly observes API structure while avoiding direct detection of diluent signals.
3Loss of information
If nuclear spin manipulation is applied to identify crystal structure, then chemical structure information can be obtained, but the measurement time and complexity increase significantly
Solution Approach 1:
The patent applies preliminary action by pre-selecting and isolating the crystal particles of interest before performing detailed spin manipulation and NMR measurement. This preliminary isolation step reduces the total number of spins that need to be manipulated and measured, thereby reducing measurement time while preserving all necessary chemical structure information for the target crystals.
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 precise acquisition of NMR information from the active pharmaceutical ingredient without interference from diluent components, allowing for accurate analysis of the crystal structure, applicable to both pharmaceutical drugs and other materials like amorphous substances or polymer blends.
Implementation Method 1
A nuclear magnetic resonance (NMR) measurement apparatus is an apparatus in which an electromagnetic wave is irradiated onto a sample, and the NMR which is caused in the sample is observed
Implementation Method 2
after the initial magnetization of the nearby hydrogen atoms is spread to peripheral hydrogen atoms which exist at a periphery of the nearby hydrogen atoms in the particle of interest
Data Source
Figure 1
Figure 2(A)~2(B)
Figure 3(A)~3(B)
AI summary
Nuclear spins of particular atoms (14N) (43) which distinctively exist in a crystal of an active pharmaceutical ingredient (32) is manipulated, so that an initial magnetization (modulated magnetization) is caused in nearby hydrogen atoms (44) which exist near the particular atoms (43) in the crystal (32). The initial magnetization of the nearby hydrogen atoms (44) is spread to peripheral hydrogen atoms (46) which exist at a periphery of the nearby hydrogen atoms (44) in the crystal (32). A magnetization which is spread in the crystal (32) is directly or indirectly observed.