Serum Albumin Complex Separation for Breast Cancer Detection

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Solution Overview

Problem

Current methods for detecting low-abundance disease proteins, such as those associated with cancer, are hindered by the dominance of high-abundance proteins like serum albumin, which masks these biomarkers and requires costly and time-consuming depletion processes, often resulting in sample loss and protein degradation.

Innovation Solution

A method involving two-dimensional membrane electrophoresis to separate serum albumin complexes directly on a protein blotting membrane, allowing for the identification of disease-specific markers by comparing reference and diseased separation profiles, enabling early detection of breast cancer stages.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If immunoaffinity chromatography is used to remove high-abundance proteins, then the number of detectable proteins increases, but sample loss and protein degradation occur due to extensive sample handling

Engineering Contradiction:
Improvenumber of detectable proteinsVSAvoidsample loss
Core Design Contradiction:
Quantity of substanceVSLoss of substance

Solution Approach 1:

The patent extracts and removes high-abundance proteins (albumin, immunoglobulins, transferrin) from serum samples using immunoaffinity depletion technology. This extraction of interfering substances enables detection of low-abundance disease markers that would otherwise be masked, directly resolving the contradiction by removing the dominant proteins while preserving the target analytes through optimized handling protocols

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary removal of high-abundance proteins before detection analysis. By depleting albumin and other abundant proteins in advance, the method prevents masking effects and reduces the need for extensive subsequent sample handling, thereby minimizing sample loss and degradation while enabling detection of low-abundance markers

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If immunoaffinity chromatography is used to remove high-abundance proteins, then the number of detectable proteins increases, but the process is time-consuming and expensive

Engineering Contradiction:
Improvenumber of detectable proteinsVSAvoiddepletion process time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The patent employs a multi-functional immunoaffinity depletion approach that simultaneously removes multiple high-abundance proteins (albumin, immunoglobulins, transferrin, haptoglobin) in a single processing step. This universal depletion method increases the number of detectable proteins while reducing the number of separate processing steps required, thereby decreasing overall processing time and cost

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Measurement precision

If depletion of high-abundance proteins is performed, then low-abundance proteins become detectable, but many potential marker proteins are removed along with the abundant proteins

Engineering Contradiction:
Improvedetection of low-abundance proteinsVSAvoidloss of marker proteins
Core Design Contradiction:
Measurement precisionVSLoss of substance

Solution Approach 1:

The patent applies localized quality control by using specific immunoaffinity reagents that selectively target only high-abundance proteins (albumin, immunoglobulins, transferrin) for removal, while preserving low-abundance disease markers. This selective local action ensures that depletion occurs only where needed (at the level of abundant proteins) without affecting the integrity or presence of potential marker proteins

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses immunoaffinity columns as intermediary devices that selectively bind and remove high-abundance proteins while allowing low-abundance markers to pass through. These intermediary reagents act as mediators that differentiate between abundant and scarce proteins based on their specific binding properties, enabling selective depletion without loss of marker proteins

Inventive Principle:
Principle #24Intermediary (Mediator)

4Quantity of substance

If extensive sample handling is performed during depletion, then high-abundance proteins are removed, but the chance of sample loss and protein degradation increases

Engineering Contradiction:
Improveremoval of abundant proteinsVSAvoidsample integrity
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent performs preliminary removal of high-abundance proteins in a optimized single-step process that minimizes subsequent handling requirements. By depleting abundant proteins early in the workflow, the method reduces the number of transfer and manipulation steps needed for subsequent detection, thereby maintaining sample integrity and reducing degradation risks

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs self-service mechanisms where the immunoaffinity depletion process is designed to be automated or self-contained, minimizing manual intervention. The depletion columns and reagents are engineered to perform the removal function with minimal user handling, reducing opportunities for sample loss or degradation while effectively removing abundant proteins

Inventive Principle:
Principle #25Self-service

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 identifies and differentiates breast cancer stages by detecting subtle changes in serum albumin complexes, providing a more reliable and efficient method for early cancer detection and treatment planning.

Implementation Method 1

the serum albumin complexes are separated by a two-dimensional electrophoresis directly on a protein blotting membrane

Methodology Applied
Scientific EffectElectrophoresis: Electrophoresis

Data Source

PatentUS9140704B2Serum markers associated with early and other stages of breast cancer
Publication Date: 2015.09.22 TEMPLE UNIV
  • US9140704B2 patent drawing
  • US9140704B2 patent drawing
  • US9140704B2 patent drawing

AI summary

Methods for identifying disease-specific markers, in particular breast cancer markers, by electrophoretically separating serum albumin complexes in a biological sample on a membrane are provided. Electrophoretic separation profiles representing different diseases or different cancer stages can be produced, and used in the diagnosis, prognosis and treatment of these diseases. Methods for identification of a cancer peptide fragment comprising a cancer peptide motif are provided. Also provided are breast cancer and other cancer markers and antibodies that specifically recognize these markers.