Ligand Concentration Detection Using Segmented Diffusion Volumes

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Solution Overview

Problem

Existing methods for measuring ligand concentration are limited to a specific range, making it difficult to accurately determine concentrations outside this range, especially when measuring multiple ligands simultaneously.

Innovation Solution

The method involves bringing a sample into contact with test sites for a predetermined time, allowing diffusion volumes of varying sizes to interact with immobilized receptors, and recording measurement signals after the interaction, which allows for precise determination of ligand concentration over a wide range by comparing signals with a reference value.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a single test site with fixed diffusion volume is used, then the measurement is simple and device structure is straightforward, but the measuring range is limited and cannot accurately determine concentrations outside the predetermined range

Engineering Contradiction:
Improveligand concentration measurement precisionVSAvoidmeasuring range
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The invention divides the single test site into multiple test sites (first test site and second test site), each with different diffusion volumes. The first test site has a larger diffusion volume for detecting low concentrations, while the second test site has a smaller diffusion volume for detecting high concentrations. This segmentation allows the system to cover a wide concentration range by selecting appropriate test sites based on the expected concentration level.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the device (different test sites) are given different properties - specifically, different diffusion volumes. The first test site is designed with a larger diffusion volume optimized for low concentration detection, while the second test site has a smaller diffusion volume optimized for high concentration detection. This local differentiation enables each region to excel at specific concentration ranges.

Inventive Principle:
Principle #3Local quality

2Adaptability or versatility

If multiple test sites with different diffusion volumes are used, then the measuring range is expanded, but the device structure and measurement process become more complex

Engineering Contradiction:
Improvemeasuring rangeVSAvoiddevice structure
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

Multiple test sites with different diffusion volumes are integrated into a single device structure. The device combines the first test site with larger diffusion volume and the second test site with smaller diffusion volume in one unit, allowing simultaneous preparation of multiple test conditions without requiring separate devices. This merging approach expands measuring range while controlling device complexity.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The device is designed to perform multiple functions - it can detect both low concentrations (using the first test site) and high concentrations (using the second test site) within a single device. This multi-functionality eliminates the need for separate devices for different concentration ranges, expanding versatility without proportionally increasing complexity.

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

3Adaptability or versatility

If multiple test sites with different diffusion volumes are used, then the measuring range is expanded, but the measurement and evaluation process becomes more complex

Engineering Contradiction:
Improvemeasuring rangeVSAvoidmeasurement process
Core Design Contradiction:
Adaptability or versatilityVSEase of operation

Solution Approach 1:

The evaluation device automatically selects which test site result to use based on feedback from the measurement process. It compares the measured concentration with the expected concentration range and selects the appropriate test site data (first or second test site) for final evaluation. This automated feedback mechanism simplifies the operation despite having multiple test sites, as the system intelligently determines which measurement to trust.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The measurement process is made dynamic by allowing the system to adaptively select between different test sites based on the measurement results. Rather than using a fixed single test site, the system dynamically chooses which test site data to rely on for the final concentration determination, optimizing the measurement process for the actual concentration present in the sample.

Inventive Principle:
Principle #15Dynamics

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 enables precise measurement of ligand concentration across a wide range by utilizing differently sized diffusion volumes and reference values, ensuring accurate results even when concentrations are outside the initial measuring range.

Implementation Method 1

diffusion volumes of different sizes adjoin the receptors immobilized on the test sites, from which the at least one ligand can diffuse to the receptor in question during the predetermined period of time

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP1980854B1Method and device for determining the ligand concentration in a sample under investigation
Publication Date: 2009.10.07 MICRONAS HOLDING GMBH
  • EP1980854B1 patent drawingFigure 1
  • EP1980854B1 patent drawingFigure 2
  • EP1980854B1 patent drawingFigure 3

AI summary

The method for determining concentration of ligands (2) contained in a sample to be analyzed, comprises arranging two test sites (7) at a surface of a carrier, immobilizing a receptor (8) suited to bind during contacting the ligands specifically to the test sites, and contacting the sample with the test sites for a pre-determined time duration, so that different large diffusion volumes adjoin in the sample to the receptor immobilized at the test sites. The ligands are diffused from the diffusion volumes to the concerned receptor during the pre-determined time duration. The method for determining concentration of ligands (2) contained in a sample to be analyzed, comprises arranging two test sites (7) at a surface of a carrier, immobilizing a receptor (8) suited to bind during contacting the ligands specifically to the test sites, and contacting the sample with the test sites for a pre-determined time duration, so that different large diffusion volumes adjoin in the sample to the receptor immobilized at the test sites. The ligands are diffused from the diffusion volumes to the concerned receptor during the pre-determined time duration, when the ligands are contained in the diffusion volumes. A measuring signal is seized for the quantity or the density of the binding events in the test sites at the end of each test sites. The measured values are compared with a given reference value or reference region. The concentration of the ligands is determined with the help of the measuring signal, which has a small interval to the reference valve or the reference value region or corresponds to the reference valve or the reference value region. The reference value region is 40-60% of the measuring signal. The measuring signal is measured at the test sites, if all the receptors of the test sites are bounded to the ligands. The reference value corresponds to a reversal point of a sigmoidal calibration curve, which assigns different values for the ligands concentration of a measured value for the test sites. The diffusion volumes are formed by a limiting wall, which limits the distance at the test sites on the sample. The sample is arranged with a different height level in the individual test sites. An independent claim is included for a device for determining concentration of ligands contained in a sample to be analyzed.