Analytical Method Using Density-Gradient Bead Washing

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing analytical methods face challenges in efficiently interacting and separating analytes and tracer substances in heterogeneous assays, particularly with solid phases like porous membranes and packed bead columns, which lead to unspecific binding and reduced reproducibility and sensitivity due to difficulties in washing out unbound tracer substances.

Innovation Solution

A method involving beads with specific densities, where the binding step forms quantifiable bead complexes, and a washing step uses a liquid medium with a higher density to disperse and separate the beads, allowing for efficient separation of unbound tracer substances by altering the centrifugal force direction, thereby releasing trapped substances and improving assay reliability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If porous membranes are used as solid phase to increase surface area for binding, then binding efficiency is improved, but washing becomes difficult due to unspecific binding and entrapment of tracer substance in pocket-like structures

Engineering Contradiction:

Improvebinding efficiencyVSAvoidwashing difficulty

Core Design Contradiction:

Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent uses porous beads as the solid phase material, which provides high surface area for capturing molecule attachment while avoiding the pocket-like structures of membranes that trap tracer substances. The porous structure of the beads allows for efficient binding without the entrapment issues encountered with planar porous membranes.

Inventive Principle:

Principle #31Porous materials

Solution Approach 2:

Instead of using planar membranes where washing is difficult, the patent inverts the approach by using spherical porous beads that can be easily suspended and washed. The three-dimensional spherical geometry allows washing solution to access all surfaces equally, eliminating the pocket-like entrapment problem of flat membranes.

Inventive Principle:

Principle #13The other way round (Inversion)

2Productivity

If beads are packed in a column structure to facilitate washing by liquid flow, then washing efficiency is improved, but tracer substances may still be trapped in interstitial spaces reducing reproducibility

Engineering Contradiction:

Improvewashing efficiencyVSAvoidassay reproducibility

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent employs dynamic washing where beads are suspended in washing solution and subjected to rotation or agitation. This dynamic approach ensures that all bead surfaces are continuously exposed to the washing solution, effectively removing trapped tracer substances from interstitial spaces that would be inaccessible in static packed columns.

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent uses hydraulic washing methods where washing solution flows through or around the bead suspension. This hydraulic approach, combined with rotation, ensures complete coverage of bead surfaces and effective removal of unbound tracer substances, improving both washing efficiency and assay reproducibility.

Inventive Principle:

Principle #29Pneumatics and hydraulics

3Measurement precision

If centrifugal force is applied to separate beads from liquid medium, then separation is improved, but direction changes are needed to release trapped substances

Engineering Contradiction:

Improveseparation efficiencyVSAvoidoperation complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs periodic changes in centrifugal force direction during the washing process. By alternating the direction of centrifugal force, trapped tracer substances are periodically dislodged from bead surfaces and interstitial spaces, ensuring complete removal while maintaining simple separation operation.

Inventive Principle:

Principle #19Periodic action

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 interaction between analytes and beads while facilitating effective washing, leading to more reliable and sensitive analytical results by ensuring complete separation of unbound tracer substances, thus improving the accuracy and reproducibility of assays.

Implementation Method 1

a washing step, which comprises: c) dispersing the packed beads in a liquid medium having a density d>m2 and m1

Methodology Applied

Scientific EffectDensity:

Implementation Method 2

separating the liquid medium and the beads comprising the quantifiable bead complexes

Methodology Applied

Scientific EffectBuoyancy: Archimedes' Principle (Buoyancy)

Implementation Method 3

a centrifuge, and preferably a centrifuge providing means for changing the orientation of the analytical device relative to the direction of the applied centrifugal force

Methodology Applied

Scientific EffectCentrifugal force: Centrifugal Force

Data Source

PatentUS10408713B2Analytical method

Publication Date: 2019.09.10 BIOMERIEUX SA

AI summary

The present invention provides a method of analyzing a sample containing an analyte to be qualitatively and/or quantitatively determined, comprising a binding step and a washing step, wherein the binding step comprises: interacting the analyte with beads having a density m1; obtaining a structure of packed beads comprising quantifiable bead complexes having a density m2; and the washing step comprises: dispersing the packed beads in a liquid medium having a density d>m2 and m1; and separating the liquid medium and the beads comprising the quantifiable bead complexes.