Sedimentation Bioassay Density Media Noise Reduction

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Solution Overview

Problem

Existing bioassays, such as sandwich assays, face limitations in sensitivity due to insufficient signal and background noise from autofluorescence and non-specific binding of labeling substances, which can lead to false-positive signals.

Innovation Solution

The use of sedimentation techniques with density media and separation layers, along with like-charged sedimentation and detection particles, and advanced fluorescent tags like quantum dots, to enhance signal detection and reduce noise in bioassays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional sandwich assays are used, then the assay can be conducted with standard reagents and procedures, but the sensitivity is limited due to insufficient signal and background noise from autofluorescence and non-specific binding

Engineering Contradiction:
Improveassay sensitivityVSAvoidbackground noise and non-specific binding
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent introduces density media as an intermediary substance between the sample and detection system. This density medium enables separation of particles based on density differences, allowing specific analyte-containing particles to be isolated from background noise and non-specific binding elements, thereby improving signal-to-noise ratio and assay sensitivity

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the density parameter of particles by coating them with materials of specific densities. By adjusting the density of particles relative to the density media, the assay can selectively sediment target particles while leaving background noise and non-specific binding elements in the supernatant, thus improving measurement precision

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If sedimentation techniques with density media are used, then sensitivity is improved by reducing non-specific binding and background noise, but the device complexity increases due to additional components and procedures

Engineering Contradiction:
Improveassay sensitivityVSAvoidassay procedure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines multiple functions into a single density media component that simultaneously provides particle separation, noise reduction, and signal enhancement. By merging these functions into one intermediary substance rather than requiring separate steps for each function, the overall procedure complexity is mitigated while maintaining improved sensitivity

Inventive Principle:
Principle #5Merging (Combining)

3Measurement precision

If like-charged sedimentation and detection particles are used, then non-specific binding is reduced improving accuracy, but the manufacturing precision requirements increase due to charge control

Engineering Contradiction:
Improveassay accuracyVSAvoidparticle charge control
Core Design Contradiction:
Measurement precisionVSManufacturing precision

Solution Approach 1:

The patent standardizes the charge parameter of particles by using uniform coating materials and procedures. By controlling the charge as a fixed parameter through consistent manufacturing processes rather than requiring precise adjustment for each assay, the manufacturing precision burden is reduced while still achieving reduced non-specific binding and improved accuracy

Inventive Principle:
Principle #35Parameter changes

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 significantly improves the sensitivity of bioassays by reducing non-specific binding and background noise, allowing for the detection of analytes at lower concentrations and providing more accurate results.

Implementation Method 1

the sedimentation particles and the unbound detection particles are subjected to sedimentation forces so that the sedimentation particles transport through the density media

Methodology Applied
Scientific EffectSedimentation: Sedimentation

Implementation Method 2

advanced fluorescent tags like quantum dots, to enhance signal detection and reduce noise in bioassays

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS9304129B2Devices, systems, and methods for conducting assays with improved sensitivity using sedimentation
Publication Date: 2016.04.05 NATIONAL TECHNOLOGY & ENGINEERING SOLUTIONS OF SANDIA LLC
  • US9304129B2 patent drawing
  • US9304129B2 patent drawing
  • US9304129B2 patent drawing

AI summary

Embodiments of the present invention are directed toward devices, systems, and method for conducting assays using sedimentation. In one example, a method includes layering a mixture on a density medium, subjecting sedimentation particles in the mixture to sedimentation forces to cause the sedimentation particles to move to a detection area through a density medium, and detecting a target analyte in a detection region of the sedimentation channel. In some examples, the sedimentation particles and labeling agent may have like charges to reduce non-specific binding of labeling agent and sedimentation particles. In some examples, the density medium is provided with a separation layer for stabilizing the assay during storage and operation. In some examples, the sedimentation channel may be provided with a generally flat sedimentation chamber for dispersing the particle pellet over a larger surface area.