Substance Determination via Spatial Signal Discrimination

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Solution Overview

Problem

Existing substance determining apparatuses face challenges in increasing sensitivity due to non-specific binding, which generates additional signals independent of analyte presence, limiting the ability to distinguish between specific and non-specific binding and thereby affecting the accuracy of low analyte concentration measurements.

Innovation Solution

A substance determining apparatus that utilizes a sensing unit to generate signals indicative of the distance and in-plane position of particles bound to a binding surface, allowing for discrimination between specific and non-specific binding by distinguishing between different kinds of binding based on these signals, thereby improving sensitivity by isolating the signal from specifically bound particles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If the instrumental signal per bead is increased, then the signal strength for specific binding is improved, but the signal for non-specific binding is also increased, so the overall sensitivity does not improve

Engineering Contradiction:
ImprovesensitivityVSAvoidnon-specific binding signal
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent segments the binding events into distinct categories by spatial location: specific binding events occur at predefined binding sites while non-specific binding events occur elsewhere on the sensor surface. The evaluation unit separately evaluates signals from these different locations, allowing the system to distinguish and quantify specific binding signals independent of non-specific binding signals, thereby resolving the contradiction where increasing instrumental signal amplifies both specific and non-specific signals equally

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by assigning different evaluation criteria to different spatial locations on the sensor surface. Binding sites have the property of specifically binding target molecules, while other areas generate non-specific binding. The evaluation unit processes signals differently based on location: signals from binding site locations are evaluated as specific binding events, while signals from other locations are evaluated as non-specific binding events. This local differentiation allows the system to extract specific binding information even when non-specific binding signals are present and amplified

Inventive Principle:
Principle #3Local quality

2Measurement precision

If blocking processes are used to reduce non-specific binding, then the accuracy of measurement is improved, but the device complexity and cost increase

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidblocking process complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical/chemical blocking process with an optical/electronic evaluation method. Instead of using blocking agents to prevent non-specific binding physically or chemically, the system uses an evaluation unit that optically or electronically distinguishes signals from binding sites versus signals from other areas. This substitution eliminates the need for additional blocking reagents and processes while achieving the same goal of improving measurement accuracy by isolating specific binding signals

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

Solution Approach 2:

The evaluation unit acts as an intermediary between the sensor surface and the measurement result. It receives raw signals from the entire sensor surface, processes them by evaluating spatial characteristics to distinguish binding site signals from non-binding site signals, and outputs corrected measurement results. This intermediary processing step eliminates the need for blocking processes by computationally separating specific and non-specific binding contributions

Inventive Principle:
Principle #24Intermediary (Mediator)

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 the sensitivity of substance determination by accurately distinguishing between specific and non-specific binding, allowing for precise measurement of analyte concentrations even at low levels, without the need for costly blocking processes.

Implementation Method 1

The beads are detected by a technique which is based on frustrated total internal reflection (FTIR)

Methodology Applied
Scientific EffectFrustrated total internal reflection: Total Internal Reflection

Data Source

PatentEP2483661B1Substance determining apparatus and method
Publication Date: 2020.02.05 KONINKLIJKE PHILIPS NV
  • EP2483661B1 patent drawingFigure 1~3
  • EP2483661B1 patent drawingFigure 4
  • EP2483661B1 patent drawingFigure 5~7

AI summary

The invention relates to a substance determining apparatus for determining a substance within a fluid. Particles, which have attached the substance, are bound to a binding surface (30). A sensing unit (33) is adapted to generate a sensing signal being indicative of at least one of i) a distance between the particles bound on the binding surface (30) and the binding surface (30) and ii) an in-plane position of the particles bound on the binding surface. A binding discrimination unit (34) is adapted to discriminate between different kinds of binding of the particles bound on the binding surface (30) depending on the generated sensing signal. The binding discrimination unit (34) is preferentially a unit for determining the part of the sensing signal being caused by specifically bound particles and to determine the substance based on this determined part of the sensing signal.