Signal Transduction Pathway Profiling Device

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Solution Overview

Problem

Current DNA-chips that assess gene expression do not accurately reflect the functional state of proteins, which is crucial for determining cellular health, disease states, and treatment efficacy, as they do not account for post-translational modifications, binding partners, and protein interactions.

Innovation Solution

A molecular detection device with immobilized recognition molecules that assess the phosphorylated or activated state of signal transduction pathway proteins and their binding partners in cell samples, allowing for the profiling of cellular pathways and identification of therapeutic targets.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If DNA-chips are used to assess gene expression, then gene expression levels can be measured, but the functional state of proteins cannot be accurately determined

Engineering Contradiction:
Improvegene expression measurementVSAvoidprotein functional state information
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The detection device segments the complex protein analysis into multiple distinct binding sites, each targeting specific proteins or modifications (e.g., phosphorylated vs. non-phosphorylated states). This segmentation allows simultaneous measurement of multiple aspects of protein function that DNA-chips cannot capture.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces immobilized recognition molecules (antibodies, ligands) as intermediaries that specifically bind to target proteins or modifications. These intermediaries enable direct detection of protein functional states, bridging the gap between gene expression data and actual protein function.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If multiple binding sites are included to profile signal transduction pathways, then pathway status determination is improved, but device complexity increases

Engineering Contradiction:
Improvepathway status determinationVSAvoidnumber of binding sites
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The detection device is designed with multi-functionality, where a single chip contains multiple binding sites that can simultaneously detect various proteins, modifications, and interactions within signal transduction pathways. This universal approach allows comprehensive pathway profiling without requiring multiple separate devices.

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

Solution Approach 2:

The patent transitions from one-dimensional gene expression measurement to multi-dimensional protein analysis by incorporating binding sites that detect different protein states (phosphorylation, binding partners, conformation). This dimensional expansion enables simultaneous assessment of multiple pathway parameters on a single device.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Reliability

If protein networks are recapitulated using immobilized recognition molecules, then functional protein states can be assessed, but manufacturing complexity increases

Engineering Contradiction:
Improvefunctional state assessmentVSAvoiddevice fabrication
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent creates a simplified copy or model of the complex protein network by using immobilized recognition molecules that replicate key protein-protein interactions and modifications. This copying approach allows accurate functional state assessment without requiring the actual complex cellular environment, simplifying manufacturing.

Inventive Principle:
Principle #26Copying

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

Enables the determination of cellular health, drug efficacy, and toxicity, as well as the identification of therapeutic targets by recapitulating protein networks and their changing states in cells, providing early warnings of disease and treatment responses.

Implementation Method 1

a molecular detection device having a plurality of binding or reaction sites comprising a series of immobilized recognition molecules or binding reagents selected and arranged to qualitatively or quantitatively assess the status of a series of signal transduction pathway proteins

Methodology Applied
Scientific EffectMolecular recognition:

Implementation Method 2

Protein interactions are defined herein as the coupling of two or more proteins in a given space and time such that a binding reaction occurs

Methodology Applied
Scientific EffectProtein binding:

Data Source

PatentUS9335328B2Method and apparatus for signal transduction pathway profiling
Publication Date: 2016.05.10 INSTANT MEDICAL DIAGNOSTICS LLC
  • US9335328B2 patent drawing
  • US9335328B2 patent drawing
  • US9335328B2 patent drawing

AI summary

An assay device for determining the presence of analytes in a cell lysate comprises a porous support member and a plurality of binding reagents arranged and immobilized at multiple reaction sites on the support member. The binding reagents are selected and arranged to assess the status of a selected cellular signal transduction pathway/protein-protein interactive network. In a further aspect, a method for assessing the status of a signal transduction pathway comprises generating a lysate of cells, the lysate retaining one or more pathway molecules present in one or more states and the pathway molecules reflecting signal transduction events taking place in the cells. The method further includes applying the lysate to an immobilized series of binding reagents which can discriminate the pathway molecules and their states. Binding events between the pathway molecules and the binding reagents are identified and the state of the selected signal pathway is determined.