Sandwich Immunoassay Sensor Chip Flow Path Control

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Solution Overview

Problem

Biochemical reactions using sandwich immunoassay on sensor chips face challenges with non-specific adsorption due to impurities in low-concentration sample liquids, affecting measurement accuracy and repeatability, and there are difficulties in completely recovering liquids from complex flow paths, leading to inconsistent residual liquid amounts and increased non-specific adsorption.

Innovation Solution

The antigen detection method involves a sensor chip with a reaction zone, liquid discharge/suction section, and liquid-mixing section, where the sample liquid is fed until it reaches the liquid-mixing section, and the labeling liquid is not allowed to reach this section, reducing non-specific adsorption by controlling the flow paths and liquid amounts, and using a pipette for precise liquid feeding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the sample liquid is fed through the entire flow path including the liquid-mixing section, then the antigen binding reaction is ensured, but non-specific adsorption increases due to residual liquid affecting measurement accuracy

Engineering Contradiction:
Improveantigen binding reliabilityVSAvoidmeasurement accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The flow path is divided into two distinct sections: the reaction zone where sample liquid is fed for antigen binding, and the liquid-mixing section that is excluded during labeling. This segmentation allows the sample liquid to reach the liquid-mixing section for thorough mixing and binding, but prevents residual liquid from contaminating the labeling reaction, thereby resolving the contradiction between ensuring binding reliability and maintaining measurement precision.

Inventive Principle:
Principle #1Segmentation

2Productivity

If the labeling liquid is fed to the liquid-mixing section, then the labeling reaction is enhanced, but non-specific adsorption from residual sample liquid impurities increases

Engineering Contradiction:
Improvelabeling efficiencyVSAvoidnon-specific adsorption
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The harmful element (residual sample liquid containing impurities) is extracted from the system by preventing the labeling liquid from entering the liquid-mixing section. This extraction eliminates the source of non-specific adsorption while maintaining labeling efficiency through optimized liquid feeding control in the reaction zone.

Inventive Principle:
Principle #2Taking out (Extraction)

3Reliability

If the flow path structure includes a liquid-mixing section for thorough mixing, then binding reliability is improved, but liquid recovery becomes difficult and residual liquid amount varies

Engineering Contradiction:
Improvebinding reliabilityVSAvoidliquid recovery ease
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

Different sections of the flow path are assigned different functional qualities: the liquid-mixing section provides thorough mixing for reliable binding, while the reaction zone is optimized for complete liquid recovery. By controlling the labeling liquid to feed only to the reaction zone, the system leverages the local quality of each section to achieve both binding reliability and ease of liquid recovery.

Inventive Principle:
Principle #3Local quality

4Measurement precision

If the amount of residual liquid is reduced to improve measurement consistency, then measurement precision is improved, but binding reaction efficiency may be reduced

Engineering Contradiction:
Improvemeasurement repeatabilityVSAvoidbinding reaction efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The sample liquid is fed in advance to the liquid-mixing section to ensure thorough mixing and complete antigen-antibody binding before the labeling step. This preliminary action in the first reaction step ensures that by the time labeling occurs, binding is already optimized, allowing subsequent liquid recovery to focus on removing residual liquid without compromising binding efficiency.

Inventive Principle:
Principle #10Preliminary 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 improves the accuracy and repeatability of measuring low-concentration targets by minimizing non-specific adsorption, reduces the amount of labeling and washing liquids needed, and shortens the measurement time, thereby enhancing the reliability and cost-effectiveness of the antigen detection process.

Implementation Method 1

an antigen-capturing antibody is immobilized on the inner surface in the middle of a fine flow channel. The fine flow channel is supplied with a target antigen-containing sample liquid, thereby allowing the antigen contained in the sample liquid and the antigen-capturing antibody to bind with each other

Methodology Applied
Scientific EffectAntigen-antibody binding: Absorption (physical)

Implementation Method 2

a labeling liquid containing a labeling antibody is fed to the fine flow channel, thereby allowing the labeling antibody to react with the target antigen captured by the antigen-capturing antibody

Methodology Applied
Scientific EffectAntigen-antibody reaction: Absorption (physical)

Implementation Method 3

surface plasmon-field enhanced fluorescence spectroscopy (SPFS) takes place

Methodology Applied
Scientific EffectSurface plasmon-field enhanced fluorescence spectroscopy: Fluorescence

Data Source

PatentUS10591473B2Antigen detection method using sandwich immunoassay method
Publication Date: 2020.03.17 OTSUKA PHARM CO LTD
  • US10591473B2 patent drawing
  • US10591473B2 patent drawing
  • US10591473B2 patent drawing

AI summary

An antigen detection method using sandwich immunoassay includes a first reaction step of preparing a sensor chip, which includes a fine flow channel in which a reaction zone having an antigen-capturing antibody immobilized thereon is arranged, a liquid discharge/suction section and a liquid-mixing section, and subsequently feeding thereto a sample liquid so as to allow the antigen-capturing antibody to capture a target; and a second reaction step of allowing a labeling liquid containing a labeling antibody to flow into the fine flow channel so as to label the target. In the antigen detection method, the labeling liquid does not reach the liquid-mixing section. According to the antigen detection method, the accuracy and the repeatability of the target measurement can be improved.