Multisite Biosensor Array for Extended Dynamic Range Quantitation

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Solution Overview

Problem

Diagnostic tests, particularly affinity-based assays, face limitations in dynamic range, leading to challenges in accurately quantifying biomarkers across a wide range of concentrations, which restricts their applicability in detecting varying biomolecule levels in samples.

Innovation Solution

A multisite biosensor system is employed, where multiple test environments with different response curves are established to expose a sample to varying conditions, generating a combined response curve that extends over a broader concentration range, allowing for accurate quantitation of molecules of interest across multiple orders of magnitude.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If a single test environment with fixed probe density is used, then the assay is simple to operate, but the dynamic range is limited

Engineering Contradiction:
Improvedynamic rangeVSAvoidsystem complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The single test environment is segmented into multiple test sites, each with different probe molecule densities. This allows the system to handle a broader dynamic range by dividing the detection task across multiple specialized sites, resolving the contradiction between adaptability and complexity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent adds a spatial dimension to the assay by creating multiple test sites with varying probe densities arranged in an array format. This dimensional approach enables extended dynamic range without proportionally increasing operational complexity, as all sites can be processed in parallel.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Measurement precision

If high probe molecule density is used to increase sensitivity, then the limit of detection is improved, but the upper limit of quantitation is reduced

Engineering Contradiction:
Improvelimit of detectionVSAvoidupper limit of quantitation
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

Different regions (test sites) of the array are assigned different probe densities optimized for specific concentration ranges. High-density sites detect low concentrations with high sensitivity, while low-density sites detect high concentrations without saturation, resolving the trade-off between detection limit and quantitation range.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The probe density parameter is varied across different test sites to create a gradient of sensitivities. This parameter change allows the system to maintain optimal detection characteristics across a wide concentration range, simultaneously improving both limit of detection and upper limit of quantitation.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If multiple test sites with different response curves are used to extend dynamic range, then quantitation accuracy is improved, but the device complexity increases

Engineering Contradiction:
Improvequantitation accuracyVSAvoidnumber of test sites
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

Multiple test sites with different response curves are merged into a single integrated array system. The combined output of all sites provides extended dynamic range and improved quantitation accuracy, while the merging approach allows for standardized processing that mitigates the increase in operational complexity.

Inventive Principle:
Principle #5Merging (Combining)

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 reliable quantitation of biomarkers over an extended range, overcoming the limitations of single-site assays by providing a linear relationship between signal and concentration, thus enhancing the sensitivity and accuracy of diagnostic tests.

Implementation Method 1

affinity probe molecules specific to a molecule of interest

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Data Source

PatentUS11143651B2Array with extended dynamic range and associated method
Publication Date: 2021.10.12 ROBERT BOSCH GMBH
  • US11143651B2 patent drawing
  • US11143651B2 patent drawing
  • US11143651B2 patent drawing

AI summary

A system and method of quantitating the concentration of a molecule of interest in one embodiment includes establishing a plurality of test environments at a plurality of test sites, each of the plurality of test environments associated with one of a plurality of response curves, each of the plurality of response curves different from the other of the plurality of response curves, storing a combined response curve resulting from a summation of the plurality of response curves, exposing the plurality of test sites to a sample having a concentration of a molecule of interest, obtaining a plurality of quantitation signals, each of the plurality of quantitation signals associated with one of the plurality of test sites, associating a summation of the plurality of quantitation signals with the stored combined response curve, and generating a signal related to the concentration of the molecule of interest based upon the association.