NMR Spectroscopy Biomarker Detection for SARS-CoV-2 Diagnosis

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current diagnostic methods for SARS-CoV-2 infection and related inflammatory conditions lack accuracy and sensitivity, particularly in early-stage detection and monitoring of disease severity and recovery, and there is a need for novel biomarkers to assess cardiovascular risks.

Innovation Solution

Nuclear Magnetic Resonance (NMR) spectroscopy-based metabolic phenotyping using Diffusion and Relaxation Editing (DIRE) pulse sequences, along with additional editing techniques like J-coupling editing, to identify unique biomarker signatures in plasma samples, including composite N-acetyl signals from glycoproteins and supramolecular phospholipid composite signals, which differentiate between healthy and SARS-CoV-2 positive patients.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional diagnostic methods are used for SARS-CoV-2 infection, then the diagnostic process is simple, but the accuracy and sensitivity are insufficient particularly in early-stage detection

Engineering Contradiction:
Improvediagnostic accuracyVSAvoiddiagnostic method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by utilizing multiple NMR spectroscopy parameters including diffusion coefficients, relaxation times (T1 and T2), and chemical shift values to characterize plasma metabolites. By measuring these physical and chemical parameters of molecular interactions, the method achieves high diagnostic accuracy for SARS-CoV-2 infection and inflammatory conditions without requiring complex additional equipment, thus resolving the contradiction between measurement precision and device complexity.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If physical NMR procedures are used to extract metabolite information, then detection capability is enhanced, but the sample cannot be retained for further experimentation

Engineering Contradiction:
Improvemetabolite detection capabilityVSAvoidsample retention
Core Design Contradiction:
Measurement precisionVSLoss of substance

Solution Approach 1:

The patent replaces mechanical separation methods with non-invasive NMR spectroscopy that interrogates molecular interactions in the native plasma state. The method uses pulse sequences (such as diffusion-edited, relaxation-edited, and combined DIRE) to extract diagnostic information about metabolites and molecular dynamics without physically altering or consuming the sample, thereby maintaining measurement precision while preserving the sample for further analysis.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Loss of information

If multiple NMR methods are applied to extract biomarker information, then diagnostic information is enriched, but the measurement time and complexity increase

Engineering Contradiction:
Improvebiomarker information extractionVSAvoidmeasurement time
Core Design Contradiction:
Loss of informationVSLoss of time

Solution Approach 1:

The patent merges multiple NMR pulse sequences (diffusion-edited, relaxation-edited, and combined DIRE) into an integrated measurement approach that simultaneously extracts multiple types of biomarker information including metabolite concentrations, molecular mobility, and relaxation characteristics. By combining these methods rather than applying them sequentially, the patent enriches diagnostic information while minimizing total measurement time, thus resolving the contradiction between information extraction and time loss.

Inventive Principle:
Principle #5Merging (Combining)

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 method provides clear and sensitive molecular signatures for diagnosing SARS-CoV-2 infection and assessing cardiovascular risks, with significant differences in biomarker intensities and ratios between healthy and infected individuals, enhancing current diagnostic capabilities and monitoring of disease recovery.

Implementation Method 1

Nuclear Magnetic Resonance (NMR) spectroscopy-based metabolic phenotyping using Diffusion and Relaxation Editing (DIRE) pulse sequences

Methodology Applied
Scientific EffectNuclear Magnetic Resonance:

Data Source

PatentUS20240402273A1Infection diagnosis and characterization using diffusion and relaxation edited proton NMR spectroscopy
Publication Date: 2024.12.05 BRUKER BIOSPIN MRI GMBH
  • US20240402273A1 patent drawing
  • US20240402273A1 patent drawing
  • US20240402273A1 patent drawing

AI summary

1H-NMR spectroscopic molecular markers are provided for identifying medical risk signatures such as SARS-CoV-2 infection, acute inflammation, or a cardiovascular risk condition. The markers use a combination of NMR intensity signals, including a Glyc signal from at least one N-acetyl (—NCOCH3) glycoprotein and an SPC signal from a choline head group (+N—(CH3)3) of a supramolecular phospholipids cluster (SPC) present in HDL and LDL lipoprotein subfractions. The Glyc signal is in a chemical shift region from #=2.00 ppm to #=2.20 ppm, and includes signals GlycA (2.00 ppm to 2.09 ppm) and GlycB (2.09 ppm to 2.2 ppm). The SPC signal is in a chemical shift region from #=3.20 ppm to #=3.30 ppm, and includes signals SPC1 (3.2 ppm to 3.235) ppm, SPC2 (3.235 ppm to 3.26 ppm), and SPC3 (3.26 ppm to 3.3 ppm). A system for identifying the markers is also provided.