Lipid-Layer Immunosensing With MTJ Readout for Specific Analyte Detection

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Solution Overview

Problem

Sandwich ELISAs face challenges with sensitivity and specificity due to fragile immune complexes and potential false positive signals from undesired binding of detection antibodies, limiting their reliability in diagnostic applications.

Innovation Solution

A method involving a sensor element with an anchor layer, a first binding agent anchored on the layer, a second binding agent with a magnetic label immobilized on a solid support, and a magnetic tunnel junction in proximity to generate a signal upon specific binding of the analyte, allowing for the detection of the analyte through altered signal changes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If sandwich ELISA format is used with immobilized capture antibody and detection antibody, then analyte detection capability is achieved, but false positive signals occur due to undesired binding of detection antibodies

Engineering Contradiction:
Improvedetection accuracyVSAvoidsignal reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent replaces the optical detection system (spectrophotometry) with a magnetic detection system using magnetic tunnel junctions (MTJ). The MTJ detects magnetic labels attached to immune complexes, providing a different physical detection mechanism that reduces false positives from undesired antibody binding while maintaining detection capability.

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

Solution Approach 2:

The patent changes the detection parameter from optical properties (light transmission) to magnetic properties. By using magnetic labels and MTJ detection, the system measures magnetic signal changes instead of optical changes, improving reliability by eliminating interference from optical background noise and undesired binding events.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If multiple reagents are sequentially added and incubated in ELISA, then analyte detection is achieved, but background noise increases reducing sensitivity

Engineering Contradiction:
Improvedetection sensitivityVSAvoidbackground noise
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent extracts the detection function from the complex multi-step ELISA process by using a solid support with integrated magnetic labels. The magnetic label is directly associated with the immune complex formation on the solid support, allowing detection without requiring multiple sequential reagent additions and incubations that generate background noise.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces magnetic labels as intermediaries that directly report immune complex formation. These magnetic labels serve as a clean signal source that is not affected by the complex chemical reactions and multiple reagent additions in traditional ELISA, thereby reducing background noise while maintaining detection sensitivity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If optical detection by spectrophotometry is used, then quantitative readout is achieved, but detection sensitivity is limited by signal amplification requirements

Engineering Contradiction:
Improveanalyte quantificationVSAvoiddetection sensitivity
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent replaces optical detection with magnetic detection using MTJ. This substitution eliminates the need for enzyme-based signal amplification that is required in optical ELISA, allowing direct detection of analyte quantities with higher sensitivity since magnetic signals from labels can be detected without amplification steps.

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

This approach enhances sensitivity and specificity by reducing background noise and enabling the detection of analytes with improved accuracy, including single molecule events, by utilizing a magnetic tunnel junction to signal the formation of the analyte-binding complex.

Implementation Method 1

a magnetic tunnel junction in functional proximity to the second binding agent which generates a signal elicited in proximity to the at least one magnetic label of the second binding agent

Methodology Applied
Scientific EffectMagnetic tunnel junction effect: Magnetoresistance

Data Source

PatentUS20240142441A1Method for immunosensing on a lipid layer using magnetic tunnel junctions ii
Publication Date: 2024.05.02 ROCHE DIAGNOSTICS OPERATIONS INC
  • US20240142441A1 patent drawing
  • US20240142441A1 patent drawing

AI summary

The present invention concerns the field of diagnostics. In particular, it relates to a method for determining an analyte suspected to be present in a sample comprising contacting said sample with a sensor element comprising an anchor layer which is present on a solid support, a first binding agent which is capable of specifically binding to the analyte, which is anchored in the anchor layer, a second binding agent which is capable of specifically binding to the analyte when bound to the first binding agent and which is immobilized on the solid support, said second binding agent comprising at least one magnetic label, and a magnetic tunnel junction in functional proximity to the second binding agent which generates a signal elicited in proximity to the at least one magnetic label of the second binding agent, for a time and under conditions which allow for specific binding of the analyte suspected to be present in the sample to the first binding agent and specific binding of the second binding agent to the analyte bound to the first binding agent and detecting the formation the complex of first binding agent, analyte and second binding agent based on an altered signal which is generated by the magnetic tunnel junction whereby the analyte is determined. The present invention, further, relates to a device and a kit for determining an analyte suspected to be present in a sample and to the use of said device for determining an analyte suspected to be present in a sample.