Slow Magic Angle Spinning NMR Probe for Metabolite Profiling
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Solution Overview
Problem
Current magic angle spinning (MAS) spectroscopy techniques face limitations in analyzing small biological samples due to poor spectral resolution, requirement for large tissue samples, and potential for metabolite loss during extraction, making continuous studies on single animals and metabolic profiling of small samples challenging and costly.
Innovation Solution
A slow-MAS probe with a sample spinning rotor and switchable LC resonator that rotates samples at a magic angle at low spinning rates, coupled with a 1H Phase Adjusted Spinning Sidebands (PASS) pulse sequence to suppress line broadening effects, allowing for high-resolution NMR metabolic profiling of small, intact biological samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If standard MAS spectroscopy is used for metabolic profiling, then adequate spectral resolution can be achieved, but large tissue samples (10-40 mg) are required which limits applications and increases cost
Solution Approach 1:
The patent employs dynamic sample spinning at the magic angle (54.74 degrees) relative to the B0 magnetic field to eliminate magnetic susceptibility variations and residual dipolar coupling effects. This dynamic approach enables high spectral resolution with significantly reduced sample sizes compared to static NMR techniques
Solution Approach 2:
The patent changes the orientation parameter by rotating the sample at a specific magic angle relative to the magnetic field, and adjusts spinning rates (including slow MAS at <500 Hz and fast MAS at >500 Hz) to optimize spectral resolution while minimizing sample requirements. This parameter optimization enables analysis of small samples without sacrificing measurement precision
2Measurement precision
If fast MAS spinning rates are used, then line broadening effects are reduced and spectral resolution improves, but sensitivity decreases at low spinning rates
Solution Approach 1:
The patent employs dynamic sample spinning at the magic angle to eliminate magnetic susceptibility variations and residual dipolar coupling effects. The system can operate at both slow MAS rates (<500 Hz) and fast MAS rates (>500 Hz), with the choice depending on the specific application requirements for spectral resolution versus sensitivity
Solution Approach 2:
The patent optimizes spinning rates and magic angle orientation to balance spectral resolution and sensitivity. By adjusting the spinning rate parameter and maintaining the sample at the magic angle, the system achieves high resolution while preserving sensitivity for small sample analysis
3Measurement precision
If tissue extraction is performed for NMR analysis, then metabolites can be analyzed, but metabolites are lost during extraction and time is consumed
Solution Approach 1:
The patent extracts and removes the problematic extraction step from the analytical workflow by performing direct NMR analysis on intact tissue samples. This eliminates metabolite loss during extraction while maintaining the ability to detect and profile metabolites through non-invasive NMR spectroscopy
Solution Approach 2:
The patent uses NMR spectroscopy as an intermediary technique that directly analyzes intact tissue without requiring chemical extraction. This intermediary approach preserves metabolite integrity while enabling comprehensive metabolic profiling, avoiding the losses associated with traditional extraction methods
4Measurement precision
If large numbers of animals are used for statistical data, then sufficient biostatistical data is obtained, but economic costs increase
Solution Approach 1:
The patent changes the sample size parameter from milligram to microgram/nanogram range through optimized MAS techniques. This parameter change enables high-resolution metabolic profiling of extremely small samples, reducing the number of animals required from dozens to potentially single-digit numbers while maintaining statistical power
Solution Approach 2:
The patent employs dynamic MAS spinning techniques that maximize information extraction from minimal samples. By optimizing the dynamic spinning parameters and magic angle orientation, the system achieves sufficient statistical data from reduced animal numbers, lowering both ethical and economic costs
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 non-invasive, high-resolution 1H NMR metabolic profiling of small samples, including nanoliter volumes, maintaining sample integrity and reducing the need for large sample sizes, thus facilitating continuous studies on small animals and minimizing biological and economic costs.
Implementation Method 1
The probe is configured to rotate the sample inclined at a magic angle with respect to the B0 magnetic field at a slow spinning rate
Implementation Method 2
The LC resonator when inserted in the support body inductively couples the first static RF coil to a second static RF coil positioned within the support that enhances the sample filling factor between the sample and the first RF coil and the sensitivity of samples analyzed therein
Implementation Method 3
Nuclear Magnetic Resonance (NMR) spectroscopy is a quantitative, non-destructive method that requires no, or minimal, sample preparation and is one of the leading analytical tools for metabonomics (metabolomics) research
Data Source
AI summary
A slow Magic-Angle Spinning NMR device and method are detailed that provide high resolution and high sensitivity metabolic profiling of biological samples. A new 1H-PASS sequence suppresses line broadening in the various biological samples. The device and method allow metabolic changes in small animals to be tracked through continuous investigations of minimally-invasive blood and tissue biopsy samples over a sustained period and allow intact biological objects with sizes up to a few centimeters to be studied.