Lateral Flow Immunoassay for Complement Activation Monitoring

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Solution Overview

Problem

Current complement activation assays are limited by their inability to provide real-time measurements, are prone to false positives due to sample handling issues, and require laboratory processing, making them unsuitable for point-of-care applications in traumatic injuries or inflammatory crises.

Innovation Solution

A point-of-care lateral flow immunoassay that selectively measures intact C3 and iC3b using carefully chosen antibody pairs to minimize cross-talk and reduce sample handling, allowing for rapid and accurate detection of complement activation levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional laboratory complement activation assays are used, then measurement accuracy can be maintained, but real-time monitoring capability is lost due to lengthy processing times

Engineering Contradiction:
Improvecomplement activation measurement accuracyVSAvoidassay processing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention extracts the essential measurement function from complex laboratory assays by using a lateral flow immunoassay format that isolates the key antigen-antibody binding events on a portable test strip, eliminating the need for lengthy laboratory processing while maintaining measurement accuracy for C3 and C3a detection

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces complex laboratory mechanical systems (centrifuges, washers, plate readers) with a simplified lateral flow mechanism driven by capillary action, allowing rapid sample processing and result visualization without sophisticated equipment while preserving measurement reliability

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

2Measurement precision

If extensive sample handling procedures are used in complement assays, then measurement completeness is improved, but false positive results increase due to sample activation

Engineering Contradiction:
Improvecomplement activation detection accuracyVSAvoidfalse positive results from sample handling
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The invention performs preliminary stabilization by adding complement inhibitor to the sample immediately upon collection, preventing unwanted complement activation during handling and storage before the actual measurement occurs, thereby eliminating false positives while maintaining detection accuracy

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention introduces complement inhibitor as an intermediary substance that blocks spontaneous complement activation during sample handling, allowing the sample to remain stable throughout processing while still permitting specific antigen-antibody binding for accurate C3 and C3a detection

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If rapid point-of-care testing is implemented, then real-time monitoring capability is achieved, but measurement reliability may be compromised due to reduced processing steps

Engineering Contradiction:
Improvetesting speedVSAvoidassay result accuracy
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The invention changes the physical parameters of the assay by using lateral flow migration and visual colorimetric detection instead of laboratory-based optical density measurement, enabling rapid point-of-care testing while maintaining result reliability through preserved antigen-antibody binding kinetics and included controls

Inventive Principle:
Principle #35Parameter changes

4Measurement precision

If complex antibody pairs are used to distinguish C3 from iC3b, then measurement specificity is improved, but cross-talk between markers increases

Engineering Contradiction:
Improvemarker differentiation accuracyVSAvoidantibody cross-reactivity
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The invention converts the potential harm of antibody cross-reactivity into a benefit by using it to detect C3 consumption - when antibodies bind both C3 and iC3b, the reduction in total bound antibody signal indicates C3 has been consumed and converted to C3b/C3a, providing useful diagnostic information about complement activation status

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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 near-real-time monitoring of complement activation, reducing false positives and providing immediate clinical insights to guide treatment decisions in traumatic injuries and inflammatory disorders.

Implementation Method 1

a point-of-care lateral flow immunoassay that selectively measures intact C3 and iC3b using carefully chosen antibody pairs

Methodology Applied
Scientific EffectAntigen-antibody binding:

Implementation Method 2

carefully chosen antibody pairs to minimize cross-talk and reduce sample handling

Methodology Applied
Scientific EffectSelective binding:

Data Source

PatentUS9939446B2Lateral flow immunoassay for complement activation and methods of use for point-of-care assessment of complement-associated disorders
Publication Date: 2018.04.10 KYPHA INC
  • US9939446B2 patent drawing
  • US9939446B2 patent drawing
  • US9939446B2 patent drawing

AI summary

A method for treating an individual at risk for a complement-associated disorder is provided, the method including: (a) obtaining a sample of a body fluid from the individual; (b) measuring a complement activation level in the sample via a point-of-care lateral flow immunoassay; (c) correlating the complement activation level in the sample to a risk of a complement-associated disorder by comparing the complement activation level in the sample to a reference level in a control, wherein a deviation in complement activation level in the sample compared to the reference level in the control indicates the individual is at risk for a complement-associated disorder; (d) selecting a treatment for the individual, based on the correlating of step (c); and (e) treating the individual with the treatment selected in accordance with step (d). Lateral flow immunoassays for the qualitative and quantitative point-of-care detection of complement activation and a method of monitoring an individual suffering from a complement-associated disorder are also provided herein.