Engineered Probiotic Biosensors for Non-Invasive IBD Monitoring

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Solution Overview

Problem

Current methods for detecting gastrointestinal diseases, such as inflammatory bowel disease (IBD), are invasive, costly, and lack accurate, non-invasive surveillance tools.

Innovation Solution

Engineered bacterial biosensors, specifically probiotic E. coli Nissle 1917 (EcN) strains expressing a reporter molecule linked to a calprotectin-responsive promoter, are used to detect calprotectin levels in gastrointestinal environments, enabling non-invasive monitoring of gut inflammation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If endoscopy is used for IBD disease activity surveillance, then diagnostic accuracy is improved, but invasiveness and complexity increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidinvasiveness
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent uses an engineered probiotic bacterium as an intermediary carrier that delivers a calprotectin-sensing system directly to the gastrointestinal tract. The bacterium expresses a promoter-calprotectin-reporter system that detects calprotectin levels in situ, providing accurate disease monitoring without requiring invasive endoscopic procedures. This intermediary approach bridges the gap between non-invasive stool collection and accurate disease assessment.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If endoscopy is used for IBD surveillance, then diagnostic accuracy is improved, but cost and resource requirements increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidresource requirements
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs a disposable engineered probiotic formulation that can be administered orally and transiently colonizes the gastrointestinal tract to perform disease monitoring. The probiotic bacterium serves as a temporary, single-use diagnostic tool that eliminates the need for expensive, resource-intensive endoscopic equipment and specialized medical facilities, making accurate IBD surveillance accessible in resource-limited settings.

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

3Ease of operation

If patient reported symptoms are used for disease activity assessment, then ease of monitoring is improved, but measurement precision deteriorates

Engineering Contradiction:
Improvemonitoring convenienceVSAvoiddisease activity prediction accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent enables patients to perform self-monitoring by collecting their own stool samples at home, which are then analyzed using a simple assay for calprotectin levels. This self-service approach empowers patients to accurately assess their own disease activity without requiring clinical visits or subjective symptom reporting, combining the convenience of home monitoring with objective, precise biomarker measurement.

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 biosensors demonstrate high sensitivity and specificity in detecting calprotectin, allowing for reliable differentiation between active IBD and remission or non-IBD states, and can be used for real-time monitoring of disease activity.

Implementation Method 1

Calprotectin is a heterodimeric protein with high affinity for zinc and other divalent cations

Methodology Applied
Scientific EffectZinc chelation:

Implementation Method 2

the reporter molecule comprises a fluorescent reporter molecule

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

the reporter molecule comprises a bioluminescent reporter molecule

Methodology Applied
Scientific EffectBioluminescence: Bioluminescence

Implementation Method 4

the reporter molecule comprises a colorimetric reporter molecule

Methodology Applied
Scientific EffectColorimetric reaction:

Data Source

PatentUS20250034613A1Engineered probiotics for detection of gastrointestinal disease in humans
Publication Date: 2025.01.30 NORTHWESTERN UNIV
  • US20250034613A1 patent drawing
  • US20250034613A1 patent drawing
  • US20250034613A1 patent drawing

AI summary

Provided herein are engineered bacterial biosensors and methods of use thereof for detection of gastrointestinal disease, including inflammatory bowel disease.