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
Engineering 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
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.
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.
2Measurement precision
If skilled personnel are required for leukemia diagnosis, then measurement precision is improved, but ease of operation decreases
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.
3Productivity
If no systemic screening tools are available, then productivity is improved (no unnecessary testing), but measurement precision worsens (cannot detect early cases)
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.
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
Implementation Method 2
cell surface phenotyping are indistinguishable from leukemia cells
Implementation Method 3
detectable by flow cytometry
Data Source
Figure 1A~1D
Figure 2A~2D
Figure 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.