Engineered Microbe-Binding Molecules for Rapid Sepsis Detection

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Solution Overview

Problem

Current diagnostic and treatment methods for sepsis are inadequate due to the lack of rapid and reliable detection techniques for microbes, particularly in medical and non-medical applications, leading to high morbidity and mortality rates.

Innovation Solution

Engineering microbe-targeting molecules with a collagen domain, Fc domain, and microbe-binding domain that provide high-affinity binding and high-sensitivity detection of microbes, enabling their use in various applications such as diagnosis, treatment, and drug delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional diagnostic methods are used for sepsis detection, then current treatment protocols can be followed, but detection speed and sensitivity are insufficient leading to delayed treatment

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent employs FcMBL (fragment crystallization domain of mannose-binding lectin) as an intermediary molecule that bridges the gap between conventional detection methods and rapid sepsis detection. FcMBL binds to microbial surfaces with high affinity, enabling sensitive detection of pathogens and microbial products in patient samples, thereby achieving both rapid and sensitive detection without requiring complex new diagnostic infrastructure

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies detection parameters by using FcMBL-based assays that can detect microbes and microbial products at very low concentrations. By changing the detection target from whole organisms to microbial components (cell wall elements, endotoxins) and using FcMBL as the binding protein, the system achieves higher sensitivity and faster detection while maintaining compatibility with existing laboratory infrastructure

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If high-affinity binding molecules are used to capture microbes, then detection sensitivity improves, but molecule design complexity increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmolecule design complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the complex microbe-binding function into distinct functional domains: the Fc domain provides structural stability and serum half-life, while the mannose-binding lectin domain provides microbial recognition. This segmentation allows independent optimization of each domain and simplifies the overall design compared to creating entirely new binding molecules

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

FcMBL serves multiple functions simultaneously: it acts as a capture agent for microbes and microbial products, provides high-sensitivity detection capability, and maintains serum half-life through Fc domain characteristics. This multi-functionality reduces the need for multiple separate reagents and simplifies the overall detection system

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Productivity

If rapid detection methods are implemented for sepsis, then treatment effectiveness improves, but current methods lack reliability and consistency

Engineering Contradiction:
Improvedetection speedVSAvoiddetection reliability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The FcMBL-based detection system is designed to be self-service in that FcMBL naturally binds to microbial surfaces and microbial products without requiring additional reagents or complex processing steps. The molecule performs both capture and detection functions, providing reliable and rapid results through a simple assay format that maintains consistency across different testing conditions

Inventive Principle:
Principle #25Self-service

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-binding molecules offer enhanced sensitivity and design flexibility, allowing for effective detection and removal of microbes from bodily fluids, food, water, and environmental surfaces, thereby improving patient care and preventing infections.

Implementation Method 1

the engineered microbe-binding molecules described herein provide not only high-affinity binding for capture of microbes (e.g., pathogens) and/or microbial matter

Methodology Applied
Scientific EffectHigh-affinity binding:

Data Source

PatentUS11807677B2Microbe-binding molecules and uses thereof
Publication Date: 2023.11.07 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US11807677B2 patent drawing
  • US11807677B2 patent drawing
  • US11807677B2 patent drawing

AI summary

Described herein are engineered microbe-targeting molecules, microbe-targeting articles, kits comprising the same, and uses thereof. Such microbe-targeting molecules, microbe-targeting articles, or the kits comprising the same can not only bind or capture of a microbe or microbial matter thereof, but they also have improved capability (e g, enhanced sensitivity or signal intensity) of detecting a microbe or microbial matter. Thus, the microbe-targeting molecules, microbe-targeting articles, and/or the kit described herein can be used in various applications, e.g., but not limited to assays for detection of a microbe or microbial matter, diagnostic and/or therapeutic agents for diagnosis and/or treatment of an infection caused by microbes in a subject or any environmental surface, and/or devices for removal of a microbe or microbial matter from a fluid.