Microbiome Monitoring via Protein Mass Spectrometry

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Solution Overview

Problem

Current methods for monitoring and controlling mixed microbial communities are time-consuming, expensive, and lack high-throughput approaches, making it difficult to monitor and control microbial production systems and natural consortia at the biomass/metabolic level, especially in applications like the gut microbiome where fast and specific methods are needed.

Innovation Solution

A method involving the characterization of microbial species and strains within a microbiome, using protein sequences and peptides to determine biomass contribution, with a specifically designed algorithm to extract system-relevant information from metagenomics and proteomics data, enabling rapid and quantitative monitoring using low-resolution mass spectrometry and simplified software for data analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If state of the art measurements using staining or genetic tools are used to monitor microbial communities, then species presence information is obtained, but the methods are very time consuming and generate very large data

Engineering Contradiction:
Improveinformation on actually expressed biomass/metabolic compositionVSAvoidtime consuming
Core Design Contradiction:
Loss of informationVSLoss of time

Solution Approach 1:

The patent extracts and analyzes only the protein fraction from microbial communities, specifically targeting expressed proteins rather than analyzing entire genomes or using non-specific staining. This extraction approach focuses measurement on the metabolically active component, reducing data complexity while providing direct information on actual biomass and metabolic composition.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces complex genetic analysis tools and staining methods with mass spectrometry-based proteomics. This substitution uses physical measurement of protein masses and spectra to directly quantify expressed biomass, eliminating the time-consuming steps of DNA extraction, sequencing, and complex bioinformatics analysis required by genetic tools.

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

2Measurement precision

If metaproteomics is used to obtain biomass mass protein information, then direct protein measurement is achieved, but the approach is very time consuming and requires very high resolution, expensive instrumentation and advanced bioinformatics tools

Engineering Contradiction:
Improvebiomass mass protein informationVSAvoidvery high resolution, expensive instrumentation and advanced bioinformatics tools
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the complex metaproteomics workflow into targeted protein analysis. Instead of attempting to identify and quantify all proteins in a microbial community with ultra-high resolution mass spectrometry, the method focuses on measuring total protein mass and specific protein markers, dividing the problem into manageable measurement components that require less sophisticated instrumentation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes the measurement parameters from requiring ultra-high resolution mass spectrometry with comprehensive protein identification to using lower resolution instruments that measure protein mass-to-charge ratios and intensities. This parameter change allows quantification of expressed biomass through protein abundance measurements without needing the most advanced and expensive mass spectrometers.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If comprehensive metaproteomic approaches are used to measure proteins directly, then biomass level monitoring is achieved, but the methods are highly complex and not suitable for high throughput

Engineering Contradiction:
Improvebiomass/metabolic level informationVSAvoidhigh throughput capability
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent applies partial action by measuring only the protein fraction relevant to biomass and metabolic composition rather than attempting complete proteomic characterization. This selective measurement approach maintains accuracy for the intended purpose while dramatically reducing analysis time and enabling high-throughput processing of multiple samples.

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The patent employs simpler, more affordable mass spectrometry instrumentation and analysis protocols that can be rapidly executed, replacing the need for expensive, time-intensive comprehensive metaproteomics platforms. This allows routine, high-throughput monitoring of microbial communities in research and clinical settings.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 allows for the rapid and focused quantitative monitoring of mixed microbial cultures, reducing complexity and enabling control of previously difficult-to-manage systems, providing relevant information on expressed biomass and metabolic composition, and facilitating medical applications like gut microbiome monitoring.

Implementation Method 1

typically said amount is determined using chemical analytics

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentUS20240401102A1Protein and peptide database-enabled rapid monitoring and quantification of microbes and associated products
Publication Date: 2024.12.05 TECH UNIV DELFT
  • US20240401102A1 patent drawing
  • US20240401102A1 patent drawing

AI summary

The present invention relates to a method of monitoring a microbiome, a method of controlling a reactor comprising a microbiome, or a method of determining an effect of a medicament or drug in an environment comprising a microbiome, wherein in both cases said microbiome is monitored according to said method, and to a microbiome monitoring computer program comprising instructions for monitoring a microbiome, which methods are efficient, relatively quick, and relatively cheap.