Substance Determination via Single-Molecule Binding Event Analysis

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Solution Overview

Problem

Existing methods for determining substances in fluids face challenges in accuracy due to non-specific binding events and the difficulty in distinguishing between specific and non-specific bindings, leading to increased data complexity and reduced sensitivity, especially at low analyte concentrations.

Innovation Solution

A substance determining apparatus that uses magnetic beads functionalized with attaching elements, such as antibodies, which bind to a binding surface, generating sensing signals indicative of binding events, allowing for the determination of particle arrival and desorption rates and lifetimes, and employing techniques like evanescent field microscopy to differentiate between specific and non-specific bindings, thereby improving accuracy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If particles are used to bind to the binding surface for substance determination, then the substance can be detected, but non-specific binding events occur leading to reduced measurement precision

Engineering Contradiction:
Improvesubstance determination accuracyVSAvoidnon-specific binding events
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent segments the binding events into individual detectable units by using single-molecule sensitivity to observe each binding event separately. This allows discrimination between specific and non-specific bindings by analyzing the characteristics of each segmented binding event, thereby improving measurement precision while accounting for non-specific binding effects.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs fluorescence labeling where particles emit different fluorescence signals when bound specifically versus non-specifically to the binding surface. This optical property change enables visual and measurable distinction between specific and non-specific binding events, improving substance determination accuracy by filtering out non-specific binding data.

Inventive Principle:
Principle #32Color changes

2Measurement precision

If a large amount of binding event data is collected to improve substance determination accuracy, then measurement precision increases, but device complexity increases

Engineering Contradiction:
Improvesubstance determination accuracyVSAvoiddata processing complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts only the essential characteristics from binding event data (such as binding duration, fluorescence intensity patterns, or position information) rather than processing the complete raw data set. This extraction of key features maintains measurement precision while significantly reducing data processing complexity and device requirements.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent implements real-time filtering during data collection to process only relevant binding events that meet specific criteria (such as minimum binding duration or intensity thresholds). This partial processing approach achieves sufficient measurement precision without the need to analyze every single binding event, thereby reducing overall device complexity.

Inventive Principle:
Principle #16Partial or excessive action

3Measurement precision

If traditional binding detection methods are used, then substance determination can be performed, but sensitivity is reduced especially at low analyte concentrations

Engineering Contradiction:
Improvedetection sensitivityVSAvoidanalyte concentration
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent replaces traditional bulk measurement methods with single-molecule fluorescence detection. This substitution of detection mechanism enables observation of individual binding events, providing superior sensitivity at low analyte concentrations where traditional methods would be overwhelmed by noise and unable to detect sufficient signal.

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

The apparatus enhances the accuracy of substance determination by distinguishing specific from non-specific binding events, reducing noise, and improving sensitivity, especially at low analyte concentrations, by analyzing binding events and lifetimes, resulting in more precise concentration measurements.

Implementation Method 1

The substance determining apparatus is preferentially a magnetic biosensor, wherein the particles are magnetic beads

Methodology Applied
Scientific EffectMagnetic field: Magnetic Field

Implementation Method 2

employing techniques like evanescent field microscopy to differentiate between specific and non-specific bindings

Methodology Applied
Scientific EffectEvanescent field: Total Internal Reflection

Data Source

PatentEP2513636B1Substance determining apparatus
Publication Date: 2020.08.05 SIEMENS HEALTHINEERS NEDERLAND BV
  • EP2513636B1 patent drawingFigure 1~3
  • EP2513636B1 patent drawingFigure 4
  • EP2513636B1 patent drawingFigure 5~6

AI summary

The invention relates to a substance determining apparatus for determining a substance within a fluid. Particles attach the substance and bind to a binding surface (30), wherein a sensing signal is generated depending on the bound particles. Binding events indicating a binding of a particle on the binding surface (30) are determined from the generated sensing signal, and the substance within the fluid is determined based on the determined binding events. During a procedure of determining a substance within a fluid, particles may bind to the binding surface and may leave the binding surface. Therefore, during this procedure a number of binding events can be determined being much larger than the number of bound particles. The determination of the substance within the fluid can therefore be based on a very large amount of data, thereby increasing the accuracy of determining the substance within the fluid.