Engineered Microbe-Targeting Molecules for Rapid Sepsis Diagnosis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current diagnostic methods for sepsis are slow and unreliable, requiring 18-24 hours for blood cultures and identification, leading to delayed treatment and high mortality rates, especially in cases of septic shock.
Innovation Solution
Engineering microbe-targeting molecules by fusing the carbohydrate recognition domain and neck region of carbohydrate-binding proteins with the Fc fragment of human IgG1, which are then attached to substrates like magnetic microbeads for rapid detection and removal of microbes, reducing complement activation side effects and enhancing binding capacity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of time
If traditional blood culture methods are used for sepsis diagnosis, then diagnostic accuracy is maintained, but detection time is delayed (18-24 hours)
Solution Approach 1:
The patent replaces traditional mechanical/cultivation-based detection methods with a molecular recognition system. Engineered microbe-targeting molecules use carbohydrate recognition domains to bind to microbial surface carbohydrates, enabling rapid detection without requiring 18-24 hour blood cultures. This substitution of detection mechanism dramatically reduces time loss while maintaining diagnostic accuracy.
Solution Approach 2:
The patent changes the detection parameter from microbial growth visualization to molecular binding detection. By using engineered molecules that bind to specific carbohydrate structures on microbial surfaces, the system detects microbes at the molecular level rather than requiring visible growth, thereby reducing detection time from days to minutes while preserving reliability.
2Reliability
If wild-type carbohydrate-binding proteins are used, then microbe binding capacity is achieved, but complement activation side effects occur
Solution Approach 1:
The patent extracts and removes the complement activation domain from the wild-type carbohydrate-binding protein structure. By separating the microbe binding function (carbohydrate recognition domain) from the harmful complement activation function, the engineered molecule retains microbe binding capacity while eliminating the harmful side effects of complement activation.
Solution Approach 2:
The patent converts the potentially harmful complement activation capability into a beneficial controlled response. By engineering the molecule to bind microbes with high affinity but without triggering uncontrolled complement activation, the system achieves effective microbe targeting while converting a harmful innate immune response into a controlled therapeutic action.
3Strength
If carbohydrate recognition domains are oriented toward the substrate, then substrate binding is achieved, but microbe binding capacity is reduced
Solution Approach 1:
The patent introduces asymmetric orientation of the carbohydrate recognition domains relative to the substrate. Rather than orienting domains directly toward the substrate surface, the engineered structure positions them to face away, allowing simultaneous substrate attachment and microbe binding capability. This asymmetric configuration resolves the conflict between substrate binding strength and microbe binding capacity.
Solution Approach 2:
The patent resolves the spatial conflict by utilizing three-dimensional orientation freedom. The carbohydrate recognition domains are positioned in a specific spatial arrangement where they can bind microbes effectively while the molecule itself attaches to the substrate, eliminating the need for direct domain-to-substrate orientation and preserving both binding functions.
4Productivity
If rapid detection methods are implemented, then treatment timing is improved, but diagnostic reliability may be compromised
Solution Approach 1:
The patent introduces engineered microbe-targeting molecules as intermediary detection agents. These molecules serve as mediators that rapidly bind to microbial carbohydrates with high specificity, providing both speed and reliability. The intermediary molecules amplify the detection signal while maintaining high diagnostic accuracy through their specific molecular recognition capability.
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 engineered microbe-targeting molecules enable rapid detection and removal of pathogens, facilitating timely treatment and potentially reducing mortality by providing a rapid diagnostic and therapeutic solution for sepsis.
Implementation Method 1
a microbe surface-binding domain, e.g., a carbohydrate recognition domain
Implementation Method 2
The engineered microbe-targeting molecules enable rapid detection and removal of pathogens
Data Source
AI summary
Described herein are engineered microbe-targeting or microbe-binding molecules, kits comprising the same and uses thereof. Some particular embodiments of the microbe-targeting or microbe-binding molecules comprise a carbohydrate recognition domain of mannose-binding lectin, or a fragment thereof, linked to a portion of a Fc region. In some embodiments, the microbe-targeting molecules or microbe-binding molecules can be conjugated to a substrate, e.g., a magnetic microbead, forming a microbe-targeting substrate (e.g., a microbe-targeting magnetic microbead). Such microbe-targeting molecules and/or substrates and the kits comprising the same can bind and/or capture of a microbe and/or microbial matter thereof, and can thus be used in various applications, e.g., diagnosis and/or treatment of an infection caused by microbes such as sepsis in a subject or any environmental surface. Microbe-targeting molecules and/or substrates can be regenerated after use by washing with a low pH buffer or buffer in which calcium is insoluble.