Magnetic Sensor Quantitative Binding Kinetics Analysis

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Solution Overview

Problem

Current methods for determining molecular binding kinetics are limited by the need for sensitive and high-throughput analysis, often requiring molecular labels that alter diffusion and steric phenomena, and cannot effectively capture detailed reaction kinetics and surface immobilization implications.

Innovation Solution

The development of a magnetic sensor device that includes a magnetic sensor in contact with an assay mixture containing a magnetically labeled molecule, allowing for real-time signal acquisition and quantitative determination of binding kinetic parameters such as association, dissociation, and diffusion rate constants.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If molecular labels are used to improve sensitivity for detection of rare molecules, then sensitivity is improved, but diffusion and steric phenomena are altered

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddiffusion and steric properties
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent replaces traditional optical detection methods with magnetic field-based detection using giant magnetoresistive (GMR) sensors. This substitution allows detection of magnetically labeled molecules without the labels interfering with diffusion and steric properties, as magnetic labels do not alter the physical-chemical characteristics of the molecules to the same extent as optical labels.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the detection parameter from optical signals to magnetic field signals. By detecting the magnetic field generated by magnetically labeled molecules binding to surface-bound probes, the system achieves high sensitivity while maintaining natural diffusion and steric behavior of the molecules.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If classical equilibrium methods are used for high throughput analysis, then throughput is improved, but detailed understanding of reaction kinetics and diffusion phenomena is lost

Engineering Contradiction:
ImprovethroughputVSAvoidreaction kinetics and diffusion information
Core Design Contradiction:
ProductivityVSLoss of information

Solution Approach 1:

The patent implements continuous real-time monitoring of molecular binding interactions using GMR sensors. The sensor continuously measures the magnetic field signal as molecules bind to the surface, providing uninterrupted kinetic data without requiring equilibrium conditions or interrupting the reaction process for measurements.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The system provides real-time feedback on binding kinetics by continuously monitoring the magnetic signal intensity over time. This feedback allows for dynamic analysis of association and dissociation rates, enabling detailed kinetic characterization while maintaining high throughput through automated data collection and analysis.

Inventive Principle:
Principle #23Feedback

3Measurement precision

If surface immobilization is used for sensing, then sensitivity is improved, but implications for reaction kinetics and diffusion are not fully captured

Engineering Contradiction:
Improvesensing sensitivityVSAvoidkinetics and diffusion implications
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The GMR sensor enables continuous monitoring of binding events at the surface without interrupting the reaction or diffusion processes. The real-time signal acquisition captures the complete time course of association and dissociation, preserving kinetic information that would be lost in endpoint equilibrium measurements.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

By replacing traditional optical detection with magnetic field detection, the system minimizes the impact of surface immobilization on molecular behavior. Magnetic labels do not significantly alter diffusion coefficients or steric properties, allowing more accurate measurement of intrinsic kinetic parameters even when molecules are surface-bound.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 accurate and sensitive measurement of molecular binding kinetics, providing detailed insights into molecular interactions without the limitations of traditional methods, with the magnetic sensor device effectively detecting and quantifying binding parameters across various concentrations and conditions.

Implementation Method 1

producing a magnetic sensor device including a magnetic sensor in contact with an assay mixture including a magnetically labeled molecule to produce a detectable molecular binding interaction

Methodology Applied
Scientific EffectMagnetic field detection: Magnetic Field

Implementation Method 2

A third kinetic parameter of interest is the diffusion rate constant, kM, which is a mathematical constant describing the rate at which labeled molecules diffuse toward a sensor

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentUS10101299B2Magnetic sensor based quantitative binding kinetics analysis
Publication Date: 2018.10.16 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US10101299B2 patent drawing
  • US10101299B2 patent drawing
  • US10101299B2 patent drawing

AI summary

Methods for quantitatively determining a binding kinetic parameter of a molecular binding interaction are provided. Aspects of embodiments of the methods include: producing a magnetic sensor device including a magnetic sensor in contact with an assay mixture including a magnetically labeled molecule to produce a detectable molecular binding interaction; obtaining a real-time signal from the magnetic sensor; and quantitatively determining a binding kinetics parameter of the molecular binding interaction from the real-time signal. Also provided are systems and kits configured for use in the methods.