Serum Enhanced Binding Test for Liver Dysfunction Detection

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Solution Overview

Problem

Conventional imaging and laboratory tests often lead to false-negative diagnoses of liver dysfunction, particularly in early stages of cirrhosis, necessitating a more sensitive and specific biomarker for liver health assessment.

Innovation Solution

The Serum Enhanced Binding (SEB) test measures the binding capacities of gold (Au), copper (Cu), cadmium (Cd), L-thyroxine, and dansylsarcosine to serum albumin, using inductively coupled plasma mass spectrometry (ICP-MS) or optical emission spectrometry (ICP-OES), to detect liver dysfunction by analyzing binding site modifications indicative of liver cell injuries.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional imaging and laboratory tests are used to diagnose liver dysfunction, then the diagnostic process is simple and widely available, but the sensitivity and specificity are insufficient leading to false-negative diagnoses

Engineering Contradiction:
Improvediagnostic sensitivity and specificityVSAvoidtest complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the diagnostic approach by focusing on a specific biomarker (albumin) and its specific binding sites, rather than using general conventional tests. This segmentation allows for targeted measurement of liver dysfunction through albumin's unique binding properties to substances like CoCh, enabling higher diagnostic precision without requiring complex multi-parameter systems

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses albumin as an intermediary biomarker that reflects liver dysfunction indirectly through its binding capacity changes. Instead of directly measuring liver cell integrity, the test measures albumin's binding ability to external substances (like CoCh), which serves as a mediator indicating hepatocyte health status, thus achieving high sensitivity while maintaining test simplicity

Inventive Principle:
Principle #24Intermediary (Mediator)

2Loss of time

If albumin binding function is measured to detect liver dysfunction, then early detection sensitivity is improved, but the measurement methodology becomes more complex

Engineering Contradiction:
Improvedetection timingVSAvoidmeasurement complexity
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by using albumin's pre-existing binding sites that are naturally present in serum. The binding capacity to substances like CoCh is inherently established before the test, allowing early detection of liver dysfunction without requiring complex sample preparation or modification steps. The test leverages the albumin's natural state to detect early changes in binding function

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent measures changes in albumin's binding capacity as a parameter that reflects liver dysfunction. By monitoring how albumin's ability to bind to substances like CoCh changes over time or in different disease states, the test achieves early detection sensitivity. This parameter-based approach (measuring binding capacity rather than structural changes) simplifies the measurement while maintaining high detection capability

Inventive Principle:
Principle #35Parameter changes

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 SEB test provides earlier detection of liver dysfunction with high sensitivity and specificity, distinguishing between cirrhotic and non-cirrhotic patients, and correlates with the severity of liver disease, potentially outperforming traditional biomarkers.

Implementation Method 1

using inductively coupled plasma mass spectrometry (ICP-MS) or optical emission spectrometry (ICP-OES)

Methodology Applied
Scientific EffectInductively coupled plasma mass spectrometry (ICP-MS):

Implementation Method 2

using inductively coupled plasma mass spectrometry (ICP-MS) or optical emission spectrometry (ICP-OES)

Methodology Applied
Scientific EffectInductively coupled plasma optical emission spectrometry (ICP-OES):

Data Source

PatentEP3884280B1Methods and kits for detecting liver dysfunction in a subject
Publication Date: 2024.01.17 INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
  • EP3884280B1 patent drawingFigure 1A~1B
  • EP3884280B1 patent drawingFigure 1C~1D
  • EP3884280B1 patent drawingFigure 2A~2B

AI summary

Most chronic liver diseases are notoriously asymptomatic, until cirrhosis with clinical decompensation occurs. The use of early diagnosis strategies is vital to maintain patients in a symptom-free state and to delay decompensation, and thus improve the outcome. Albumin (HAS) undergoes several post-translational modifications in hepatocytes but clinical relevance of some of these modifications has been recently investigated in advanced liver diseases. Now, the inventors demonstrate that the binding capacities of some ligands, measured by inductively coupled plasma mass spectrometry (ICP-MS), are significantly different between cirrhotic patients and patients with no liver dysfunctions. The decreased binding capacities in cirrhotic patients were paralleled by the presence of significantly higher HSA isoforms. Animal experimentations were also conducted to explore the precocity of HSA modifications in the course of chronic liver dysfunction. This allow the inventors to assume that the most important modifications of albumin structure due to liver dysfunction could be revealed by measuring the unbound fraction of specific ligands spiked in serum.