Cell Debris Marker Assay for Liquid Biopsy Protein Detection

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Solution Overview

Problem

Current methods for analyzing proteins in liquid biopsies face challenges in distinguishing disease-related proteins from those naturally present in bodily fluids, leading to inaccurate and insensitive diagnostic results for conditions like cancer.

Innovation Solution

The method involves detecting cell debris-associated target molecules by contacting a sample with binding molecules specific to cell debris markers, allowing for the identification and quantification of proteins embedded in membrane fragments, which are indicative of tumor cells or other disease states, using techniques like proximity ligation assays or mass spectrometry.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional protein detection methods are used in liquid biopsies, then the analysis can be performed with standard techniques, but the specificity and sensitivity are insufficient due to inability to distinguish disease-related proteins from naturally present proteins

Engineering Contradiction:
Improvedetection accuracyVSAvoidassay complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the detection process into two distinct stages: first capturing cell debris markers (such as phosphatidylserine or calreticulin) on beads, then detecting disease-related proteins specifically associated with those captured cell debris. This segmentation allows the assay to distinguish between naturally present proteins and disease-related proteins, significantly improving detection accuracy while maintaining manageable assay complexity through modular design

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces cell debris markers as intermediary elements that mediate between the blood sample and the disease-related proteins. By using beads coated with cell debris markers to capture and enrich cell debris containing disease-related proteins, the assay creates a selective intermediate step that enhances specificity. This intermediary approach allows standard detection techniques to achieve superior precision by focusing only on proteins associated with diseased cell debris

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If enrichment for cell debris markers is performed, then the specificity of disease marker detection is improved, but the procedure requires additional steps

Engineering Contradiction:
Improvediagnostic reliabilityVSAvoidprocedure steps
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary enrichment of cell debris markers before disease-related protein detection. By first capturing cell debris markers on beads and then detecting disease-related proteins on the enriched cell debris, the assay establishes a reliable foundation for accurate diagnosis. This preliminary action ensures that subsequent protein detection occurs specifically on disease-relevant material, significantly enhancing diagnostic reliability

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent merges multiple detection objectives into a unified workflow where cell debris marker capture and disease-related protein detection are combined in sequence. By using the same bead system for both enrichment and detection, the procedure integrates what could be separate complex steps into a coordinated assay, improving reliability while managing overall procedure complexity through functional integration

Inventive Principle:
Principle #5Merging (Combining)

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 enhances the specificity and sensitivity of protein detection in blood samples, providing more accurate diagnostic information for diseases by focusing on markers associated with cell debris and offering an alternative to invasive biopsies.

Implementation Method 1

contacting the sample or a subsample thereof with at least one binding molecule, wherein the at least one binding molecule binds a cell debris marker

Methodology Applied
Scientific EffectMolecular recognition:

Data Source

PatentUS20240345104A1Compositions and methods for assaying circulating molecules
Publication Date: 2024.10.17 GUARDANT HEALTH INC
  • US20240345104A1 patent drawing
  • US20240345104A1 patent drawing
  • US20240345104A1 patent drawing

AI summary

Provided herein are methods of detecting and quantifying target molecules associated with cell debris. Provided herein are also methods for determining the likelihood that a subject has a disease or condition, such as cancer.