Mass Spectrometric Sepsis Diagnosis Without Blood Culture Delay
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Solution Overview
Problem
Current methods for mass spectrometric identification of microbes in body fluids, particularly in cases of sepsis, are limited by the need for pure cultures and are too slow due to the low concentration of microbes, often requiring hours or days for sufficient growth, which can be critical for timely medical intervention.
Innovation Solution
A method involving immediate dissolution of human particles in body fluids using weak surfactants, followed by centrifugation or filtration to separate microbes, cultivation in a nutrient broth free of antimicrobial components, and subsequent separation and identification through mass spectrometry, accompanied by optical or spectrometric monitoring of microbial growth to determine the optimal time for mass spectrometric identification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional mass spectrometric identification methods are used with blood culture, then microbe identification can be achieved, but the process takes hours or days due to low microbe concentration requiring sufficient growth time
Solution Approach 1:
The patent applies preliminary action by performing immediate dissolution of human particles and separation of microbes from body fluids right after sampling, before cultivation. This prepares the sample in advance for rapid mass spectrometric analysis once microbes reach sufficient concentration, eliminating the need to start from scratch with whole blood samples.
Solution Approach 2:
The patent extracts microbes from body fluids by dissolving human particles with surfactants and separating the microbial component through centrifugation or filtration. This extraction isolates the microbes of interest from the complex matrix of blood or other body fluids, enabling focused cultivation and subsequent rapid detection without interference from human cells.
2Quantity of substance
If microbe concentration in body fluids is low, then identification is difficult without sufficient growth, but prolonged cultivation delays treatment
Solution Approach 1:
The patent implements feedback by optically monitoring microbial growth in real-time during cultivation. This allows the system to detect when microbes have reached sufficient concentration for mass spectrometric identification and automatically trigger the analysis, optimizing the timing without requiring fixed prolonged cultivation periods.
Solution Approach 2:
The patent changes the parameter of microbe concentration through controlled cultivation in nutrient broth, transforming the sample from low concentration in body fluids to high concentration suitable for detection. The optical monitoring tracks this parameter change to determine the optimal moment for identification.
3Ease of manufacture
If human particles are not dissolved before analysis, then sample preparation is simpler, but mass spectrometric analysis is interfered with by human proteins
Solution Approach 1:
The patent extracts microbes from body fluids by dissolving human particles with surfactants and separating the microbial component through centrifugation or filtration. This extraction isolates the microbes of interest from the complex matrix of blood or other body fluids, enabling focused cultivation and subsequent rapid detection without interference from human cells.
Solution Approach 2:
The patent uses surfactants as intermediaries to dissolve human particle membranes and release microbial components. The surfactant acts as a mediator that selectively disrupts human cell membranes while preserving microbial integrity, enabling subsequent separation and analysis.
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 faster detection and identification of microbes in body fluids, allowing for immediate targeted treatment, potentially saving lives and reducing medical costs by ensuring microbes are present in a sufficiently pure form for mass spectrometric analysis.
Implementation Method 1
immediate dissolution of human particles in body fluids using weak surfactants
Implementation Method 2
followed by centrifugation or filtration to separate microbes
Implementation Method 3
identification through mass spectrometry
Implementation Method 4
accompanied by optical or spectrometric monitoring of microbial growth
Data Source
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Figure 3
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AI summary
The invention relates to methods and instruments for the rapid detection and rapid mass spectrometric identification of microbial infective agents in blood or other body fluids. The invention recognizes that blood is not a good environment for the cultivation of microbes and provides a method which (a) largely destroys or dissolves the human particles in body fluids, such as erythrocytes and leukocytes in blood, without impairing the ability of the microbes to reproduce, (b) separates the microbial pathogens from the fluid, (c) cultivates them in a nutrient broth which contains none of the antimicrobial components of the body fluids, (d) separates them from the nutrient broth, and (e) identifies the microbes by a mass spectrum of the microbial proteins. The dissolution of the human particles also releases the microbes nesting in macrophages. The cultivation in an optically clear nutrient broth with optimum composition not only accelerates the propagation of the microbes compared to all other cultivation methods, but also makes it possible to continuously measure their quantitative growth starting from a low microbe density. This firstly allows the mass spectrometric identification to be carried out at the earliest possible time, secondly provides a positive detection of microbes far ahead of their identification, which can be lifesaving for the patient; and thirdly makes it possible to start the determination of resistances early.