Leukemia Detection via Aspergillus Flavus and EBV Induction

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Solution Overview

Problem

Current methods for diagnosing leukemia are complex, require skilled personnel, and lack definitive laboratory tests for predicting predisposition, especially in children and infants, with no systemic screening tools available for early detection or prevention of leukemias and lymphomas.

Innovation Solution

The method involves exposing mononuclear leukocyte cells to specific proteins from Aspergillus flavus and Epstein-Barr virus (EBV) in vitro, using enzyme-linked-immunosorbent serologic assay (ELISA) to detect the re-induction of cell surface markers characteristic of acute lymphoblastic leukemia (ALL), allowing for the identification of individuals at risk or in remission.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If complex diagnostic methods are used to detect leukemia, then measurement precision is improved, but device complexity increases and ease of operation decreases

Engineering Contradiction:
Improveleukemia detection accuracyVSAvoiddiagnostic procedure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and isolates specific cell surface markers (CD10, CD19, CD34, CD117) that are characteristic of leukemia cells, using monoclonal antibodies to detect only these specific markers. This extraction approach simplifies the diagnostic process by focusing on key indicators rather than comprehensive complex analysis.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs flow cytometry with fluorescently labeled monoclonal antibodies that bind to specific cell surface markers. The fluorescent signals produce distinct color changes that allow rapid visualization and quantification of leukemia-specific markers, enabling precise detection through simple optical measurement.

Inventive Principle:
Principle #32Color changes

2Measurement precision

If skilled personnel are required for leukemia diagnosis, then measurement precision is improved, but ease of operation decreases

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidoperational simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent uses monoclonal antibodies that automatically and specifically bind to their target cell surface markers without requiring manual identification or interpretation by skilled personnel. The flow cytometry instrument automatically analyzes the fluorescent signals and provides quantitative results, making the diagnostic process self-executing and reducing dependence on expert operators.

Inventive Principle:
Principle #25Self-service

3Productivity

If no systemic screening tools are available, then productivity is improved (no unnecessary testing), but measurement precision worsens (cannot detect early cases)

Engineering Contradiction:
Improvescreening efficiencyVSAvoidearly detection capability
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent enables preliminary screening of asymptomatic individuals by detecting the presence of leukemia-specific cell surface markers before clinical symptoms appear. The flow cytometry assay can identify abnormal marker expression patterns in peripheral blood samples, allowing early detection and intervention before the disease progresses.

Inventive Principle:
Principle #10Preliminary action

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

This approach effectively discriminates between individuals with a history of leukemia and healthy controls, providing a potential tool for mass screening and early detection of leukemia susceptibility, with the combination of Aspergillus flavus and EBV inducing specific cell surface markers detectable by flow cytometry.

Implementation Method 1

enzyme-linked-immunosorbent serologic assay (ELISA) to detect the re-induction of cell surface markers

Methodology Applied
Scientific EffectAntibody-antigen binding:

Implementation Method 2

cell surface phenotyping are indistinguishable from leukemia cells

Methodology Applied
Scientific EffectLight scattering:

Implementation Method 3

detectable by flow cytometry

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP2656076B1Methods of detecting leukemia/ lymphoma and induction of the same
Publication Date: 2017.11.01 TEBBI CAMERON K
  • EP2656076B1 patent drawingFigure 1A~1D
  • EP2656076B1 patent drawingFigure 2A~2D
  • EP2656076B1 patent drawingFigure 3A~3C

AI summary

A diagnostic test is described using aspergillus flavus fungal cultures, EBV or their combination to induce leukemic cell surface markers in mononuclear cells of former or current leukemia patients. Detection of the leukemic transformation by means known in the art, identified patients who have or had leukemia, or potentially may become leukemic. Unlike aflotoxin, which indiscriminately induces leukemic transformation, the compositions used were specific to leukemia-predisposed patients, but not other cancers or normal controls. The test identifies survivors of ALL and can detect propensity for development of leukemia in susceptible individuals. An ELISA technique using the described fungal products or EBV and combination can detect individuals with history of leukemia and not controls. These findings have implications for the etiology of leukemias and lymphomas. This invention can potentially be used for mass screening, detection of susceptible individuals to leukemia and ultimately their vaccination.