Lateral Flow Assay for Peritoneal Dialysate Biomarker Detection

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Solution Overview

Problem

Patients undergoing peritoneal dialysis face challenges in detecting early infections, which can lead to damage and loss of the infusion line/catheter, resulting in high treatment costs and the need for surgical intervention, as current methods rely on visual changes or aromas, lacking reliable detection mechanisms.

Innovation Solution

A method that integrates with PD fluid-handling equipment to test waste fluid for markers such as MMP8, IL-6, and other biomarkers in peritoneal dialysate, providing early detection of peritonitis through a lateral flow assay format, allowing for timely corrective action and reducing healthcare costs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If visual inspection or aroma detection is used to detect infection, then the detection method is simple and does not require complex equipment, but the detection reliability is insufficient and cannot detect early infections

Engineering Contradiction:
Improvedetection reliabilityVSAvoiddetection method complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces subjective sensory detection (visual inspection and aroma detection) with objective biochemical detection using MMP-8 enzyme activity measurement. The mechanical/sensory system of human observation is substituted with an enzymatic assay system that quantitatively measures neutrophil presence through MMP-8 activity, providing reliable early infection detection without requiring complex medical equipment.

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

Solution Approach 2:

The patent introduces MMP-8 enzyme activity as an intermediary marker to detect the presence of neutrophils and early infection. Instead of directly detecting infection or relying on subjective sensory cues, the assay uses MMP-8 as a mediator that specifically indicates neutrophil infiltration, enabling reliable and early detection of peritonitis before clinical symptoms appear.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Loss of time

If early detection of peritonitis is achieved through biomarker analysis, then treatment can be initiated earlier and line loss can be prevented, but the detection method becomes more complex and costly

Engineering Contradiction:
Improvetime to detect infectionVSAvoiddetection system complexity
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The patent extracts and measures only the specific MMP-8 enzyme activity from the complex dialysate fluid, rather than analyzing multiple parameters or using comprehensive infection workups. This focused extraction of the key biomarker (MMP-8) enables early detection with a relatively simple and cost-effective enzymatic assay, reducing the time to detection without requiring complex multi-parameter analysis systems.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary detection of MMP-8 activity in the dialysate fluid before clinical symptoms of peritonitis develop. By measuring neutrophil infiltration through MMP-8 activity early in the infection process, the system enables timely intervention and antibiotic treatment before line loss occurs, reducing the time delay between infection onset and treatment initiation.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If multiple biomarkers are analyzed to confirm peritonitis, then the diagnostic accuracy is improved, but the testing time and complexity increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidtesting time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts and measures only the critical MMP-8 enzyme activity as the primary diagnostic marker for peritonitis. Rather than simultaneously analyzing multiple biomarkers, the assay focuses on extracting and quantifying MMP-8 activity, which provides sufficient diagnostic accuracy for early peritonitis detection. This selective extraction approach maintains measurement precision while significantly reducing testing time and complexity compared to multi-marker panels.

Inventive Principle:
Principle #2Taking out (Extraction)

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 reliable and early detection of peritonitis, allowing patients to remain on peritoneal dialysis, reducing healthcare costs and extending its clinical utility by identifying increased levels of specific markers indicative of infection, thereby preventing damage and line loss.

Implementation Method 1

a lateral flow test strip which has immobilised on it reagents capable of specifically binding to one or more of the markers

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 2

reagents capable of specifically binding to one or more of the markers

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentEP3380237B1Method of detecting peritonitis
Publication Date: 2020.09.02 MOLOGIC LTD
  • EP3380237B1 patent drawingFigure 1
  • EP3380237B1 patent drawingFigure 2~4
  • EP3380237B1 patent drawingFigure 5~6

AI summary

A diagnostic test apparatus comprises: an elongate housing defining a test strip holder containing a lateral flow test strip; a fluid sampling chamber provided with an opening connecting the fluid sampling chamber with the test strip holder; a viewing window in the elongate housing allowing reading of one or more portions of the lateral flow test strip; and a connector configured to couple the diagnostic test apparatus to a bulk source of fluid. The apparatus may be included in a kit of parts. The apparatus is useful for detecting peritonitis. The bulk source of fluid may be peritoneal dialysate. Various markers may be determined in the bulk source of fluid such as MMP8, IL-6, HNE, MMP2, MMP9, TIMP1, TIMP2, NGAL, A1AT, desmosine, fibrinogen, IL-8, calprotectin, fMLP, IL1 b, cystatin C, HSA, RBP4, SPD, MPO, sICAM and TNFa. Detection of the markers to indicate peritonitis may also inform treatment choices.