Label-Free Molecular Detection via Electric Field Mobility

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Solution Overview

Problem

Current label-free detection technologies face challenges in sensitivity, particularly for small molecules, and struggle to detect conformational changes and biochemical reactions, while also being incompatible with microarray platforms for analyzing molecular interactions and mobility.

Innovation Solution

An apparatus comprising a conductive surface, a molecular bridge, electrodes, and a solution that allows for the measurement of molecular movement in an electric field, using techniques like surface plasmon resonance and total internal reflection microscopy to detect changes in distance and mobility, enabling real-time analysis of molecular interactions and reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If label-free detection technologies are used, then real-time monitoring of molecular binding is achieved, but sensitivity diminishes with the size of the molecule making it hard to detect small molecules

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmolecule size
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent introduces an intermediary approach by using a molecular bridge between the surface and the molecule, combined with electric field interaction. This intermediary mechanism enables the detection of small molecules through their mobility and charge properties rather than relying solely on mass-based detection, thereby maintaining high sensitivity across different molecule sizes.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the detection parameter from mass-based detection to mobility-based detection in an electric field. By measuring how molecules move in response to an electric field (determined by charge, mass, and other physical properties), the system achieves high sensitivity for small molecules while maintaining real-time monitoring capability.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If current label-free technologies are used, then real-time monitoring is achieved, but detection of conformational changes and biochemical reactions is difficult

Engineering Contradiction:
Improvedetection capabilityVSAvoiddetection scope
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent creates a universal detection platform that can monitor multiple types of molecular events simultaneously—binding interactions, conformational changes, and biochemical reactions—using the same electric field-based mobility detection mechanism. This multi-functional approach expands the detection scope without requiring separate specialized systems for each type of molecular analysis.

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

Solution Approach 2:

The system provides real-time feedback on molecular events through continuous monitoring of mobility changes in the electric field. This feedback mechanism enables the detection of dynamic processes such as conformational changes and biochemical reactions as they occur, rather than requiring endpoint analysis.

Inventive Principle:
Principle #23Feedback

3Measurement precision

If mobility measurement methods are used, then molecular identification based on distinct mobility is achieved, but compatibility with microarray platform is lost

Engineering Contradiction:
Improvemolecular identification accuracyVSAvoidplatform compatibility
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent segments the detection system into modular components that can be integrated with microarray platforms. The molecular bridge and electrode structure can be incorporated into microarray chips, allowing mobility-based molecular identification to be performed in a high-throughput, microarray-compatible format.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent adds a new dimension to molecular analysis by incorporating electric field-based mobility measurement into the microarray platform. This dimensional addition enables simultaneous measurement of multiple molecular properties (binding, conformational changes, mobility) on the same platform, enhancing both identification accuracy and platform versatility.

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

4Measurement precision

If isoelectric point measurement is used, then molecular charge state analysis is achieved, but compatibility with microarray platform is lost

Engineering Contradiction:
Improvecharge state detection accuracyVSAvoidplatform compatibility
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent merges the isoelectric point measurement capability with the microarray platform by integrating the electric field-based detection system into the microarray structure. This combination enables charge state analysis of molecules arrayed on the microarray surface, achieving both high measurement precision and platform compatibility simultaneously.

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 solution enhances sensitivity for detecting small molecules and conformational changes, allows for high-throughput analysis of molecular interactions and mobility, and identifies proteins based on isoelectric points, overcoming limitations of existing technologies.

Implementation Method 1

the sensor is selected from the group consisting of a surface plasmon resonance (SPR) sensor

Methodology Applied
Scientific EffectSurface plasmon resonance:

Implementation Method 2

at least one electrode configured to form an electric field between the electrode and the surface

Methodology Applied
Scientific EffectElectric field: Electric Field

Implementation Method 3

a molecular bridge configured to bind to said surface and to bind to a molecule

Methodology Applied
Scientific EffectMolecular binding:

Data Source

PatentUS11635431B2Apparatus for analyzing and detecting interactions and reactions of molecules
Publication Date: 2023.04.25 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA
  • US11635431B2 patent drawing
  • US11635431B2 patent drawing

AI summary

An apparatus for label-free analysis of molecules, including interactions and reactions of the molecules, is disclosed. The apparatus is based on detecting molecule movement under the influence of an external electric field. The apparatus is able to achieve sensitive detection of molecular binding to proteins or other molecules, and conformational changes of proteins or other molecules and biochemical reactions of the proteins or other molecules. Applications of the apparatus include screening of drug molecules, kinetic analysis of posttranslational modification of proteins, and small molecule-protein interactions.