Boronic Acid Magnetic Complex for Sialic Acid Concentration

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Solution Overview

Problem

Existing methods for detecting sialic acid in biological fluids, particularly for early cancer diagnosis, face challenges due to the trace amounts present and the inability to effectively concentrate and collect this biomarker for comprehensive cancer testing.

Innovation Solution

A complex comprising a boronic acid group with a binding constant of 500 M^-1 or more and a magnetic particle, chemically bonded through a linker, is used to selectively bind and concentrate sialic acid, followed by pH-adjusted recovery and dissociation steps to enhance detection efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional ELISA method utilizing antigen-antibody reaction is used for cancer detection, then detection of advanced cancer is effective, but detection of early cancer with trace amounts of cancer-derived components is not feasible

Engineering Contradiction:
Improvedetection sensitivityVSAvoidamount of cancer-derived component
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The invention segments the detection approach by first isolating and concentrating sialic acid from complex biological fluids using magnetic particles functionalized with boronic acid, then performing detection on the concentrated fraction. This two-stage process (concentration followed by detection) enables detection of trace amounts of cancer-derived components that would be undetectable by conventional ELISA methods alone

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention performs preliminary concentration and purification of sialic acid before the actual detection step. By using magnetic particles with boronic acid groups to selectively bind and concentrate sialic acid from biological fluids in advance, the method prepares a sufficiently concentrated sample for subsequent detection, making early cancer detection feasible

Inventive Principle:
Principle #10Preliminary action

2Measurement precision

If biomarker-specific detection method is used for each cancer species, then specific cancer detection is accurate, but comprehensive cancer testing across multiple species is not achievable

Engineering Contradiction:
Improvecancer detection accuracyVSAvoidcancer species coverage
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The invention uses sialic acid as a universal biomarker that is commonly overexpressed across multiple cancer species rather than requiring cancer-specific biomarkers. The magnetic particle complex with boronic acid can bind sialic acid from any cancer source, enabling a single platform to detect multiple cancer types simultaneously, thus achieving both accuracy and versatility

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

Solution Approach 2:

The invention introduces sialic acid as an intermediary molecule that mediates between diverse cancer cells and the detection system. Instead of requiring direct interaction between detection reagents and various cancer-specific biomarkers, the system uses sialic acid (which is universally present on cancer cell surfaces) as a common intermediary that can be captured by boronic acid-functionalized magnetic particles, enabling comprehensive cancer screening

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If boronic acid with low binding force (aminophenylboronic acid) is used for sialic acid detection, then selectivity is achieved, but binding strength is insufficient for effective concentration

Engineering Contradiction:
ImproveselectivityVSAvoidbinding force
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The invention creates a composite material by combining magnetic particles with boronic acid functional groups through a linker molecule. This composite structure integrates the selectivity of boronic acid for sialic acid with the concentration capability of magnetic particles, and the composite design optimizes the binding interaction strength while maintaining selectivity

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The invention changes the parameters of the boronic acid compound by selecting specific types (such as 5-BPA with high binding constants exceeding 1,000 M^-1) and optimizing the molecular structure through linkers. This parameter optimization enhances the binding force between the boronic acid group and sialic acid while preserving the selective recognition capability, enabling effective concentration of sialic acid

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

The method allows for the effective collection and concentration of sialic acid, enabling comprehensive cancer testing that is not species-specific, improving the detection of early cancers and enhancing patient prognosis.

Implementation Method 1

boronic acid that selectively binds to the sialic acid has been reported

Methodology Applied
Scientific EffectSelective binding: Adsorption

Implementation Method 2

A complex comprising a boronic acid group with a binding constant of 500 M^-1 or more and a magnetic particle, chemically bonded through a linker

Methodology Applied
Scientific EffectChemical bonding: Chemical Bonding

Implementation Method 3

a recovering step of separating and recovering the complex after the bonding step from the liquid sample with a magnet

Methodology Applied
Scientific EffectMagnetic separation: Magnetism

Implementation Method 4

a bonding step of bonding sialic acid to the complex of any one of the above-mentioned items <1> to <8> by adjusting a pH of a liquid sample, which contains the complex and a biological fluid containing the sialic acid, to less than 6

Methodology Applied
Scientific EffectpH-dependent binding:

Data Source

PatentEP4717350A1Complex and method for collecting sialic acid
Publication Date: 2026.04.01 NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE & TECHNOLOGY
  • EP4717350A1 patent drawingFigure 1~2
  • EP4717350A1 patent drawingFigure 3~5
  • EP4717350A1 patent drawingFigure 6(a)~7

AI summary

Provided are a complex, which can collect and concentrate sialic acid, and a method of collecting the sialic acid. A complex (1) of the present invention is represented by the following formula (1):         Ba-L-Mp     (1) where, in the formula (1), Ba represents a boronic acid group having a binding constant Ka with sialic acid of 500 M-1 or more, Mp represents a magnetic particle having ferromagnetism, and L represents a linker for bonding the boronic acid group and the magnetic particle. The complex represented by the formula (1) shows a state in which the boronic acid group and the magnetic particle are chemically bonded through the linker.