Agarose-Filled Ceramic Apatite for Biomolecule Purification

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Solution Overview

Problem

Current methods for purifying viruses, proteins conjugated to large particles, and other large biomolecules are limited by the need for expensive resins, low flow rates, and limited sample loads in size exclusion chromatography, and have limited selectivity in ion exchange and hydrophobic interaction chromatography, while centrifugation is only applicable to dense biomolecules.

Innovation Solution

A ceramic apatite bead filled with agarose is used, which maintains selectivity and binding capacity by allowing target molecules to interact with ceramic apatite via its pores, while the agarose does not significantly interfere with this interaction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If size exclusion chromatography is used for purification, then separation of large biomolecules from smaller impurities is achieved, but expensive resins are required and flow rates are limited

Engineering Contradiction:
Improvepurification effectivenessVSAvoidcolumn requirements
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines ceramic apatite beads with agarose polymer to create a composite chromatography medium. The ceramic apatite provides structural stability and selectivity for large biomolecules, while the agarose filling modifies pore properties to enhance size exclusion effects. This composite structure eliminates the need for expensive specialized resins while maintaining effective purification of large biomolecules from smaller impurities.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent utilizes the porous structure of ceramic apatite beads, filling the pores with agarose polymer. The porous material allows size-based separation where larger biomolecules are excluded from pores while smaller impurities enter and are retained. This porous mechanism provides effective purification without requiring complex column configurations or expensive resins.

Inventive Principle:
Principle #31Porous materials

2Reliability

If ion exchange chromatography or hydrophobic interaction chromatography is used, then purification is achieved, but selectivity is limited

Engineering Contradiction:
Improvepurification capabilityVSAvoidselectivity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent applies local quality by creating regions with different properties within the chromatography bead. The ceramic apatite exterior provides one type of interaction while the agarose-filled pores provide size exclusion properties. This spatial differentiation of functional properties enables high selectivity for large biomolecules, distinguishing them from smaller impurities through combined mechanisms rather than relying on limited selectivity of single-mode chromatography.

Inventive Principle:
Principle #3Local quality

3Reliability

If centrifugation is used for separation, then large dense biomolecules can be separated, but it is not applicable to less dense biomolecules

Engineering Contradiction:
Improveseparation effectivenessVSAvoidapplicability range
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent creates a universal purification medium that handles diverse biomolecules through multiple mechanisms. The ceramic apatite-agarose composite provides both size exclusion and selective binding capabilities, making it applicable to viruses, protein-nanoparticle conjugates, and other large biomolecules regardless of their density. This multi-functional approach replaces density-dependent centrifugation with a versatile chromatography system.

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

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 agarose-filled ceramic apatite effectively separates and purifies target molecules, such as protein-nanoparticle conjugates, by excluding contaminants and maintaining the selectivity and binding capacity of the ceramic apatite, even under varying conditions.

Implementation Method 1

incubating ceramic apatite in an agarose solution heated to a temperature from about 60°C to about 100 °C

Methodology Applied
Scientific EffectHeating: Heating

Implementation Method 2

cooling the heated agarose solution having ceramic apatite to between about 4 °C to about 30 °C to form an insoluble porous agarose gel within the pores of the ceramic apatite

Methodology Applied
Scientific EffectCooling: Cooling

Implementation Method 3

cooling the heated agarose solution having ceramic apatite to between about 4 °C to about 30 °C to form an insoluble porous agarose gel within the pores of the ceramic apatite

Methodology Applied
Scientific EffectGelation: Gel

Implementation Method 4

The agarose-filled ceramic apatite effectively separates and purifies target molecules, such as protein-nanoparticle conjugates, by excluding contaminants and maintaining the selectivity and binding capacity of the ceramic apatite

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentEP3519070B1Agarose-filled ceramic apatite
Publication Date: 2025.04.02 BIO RAD LABORATORIES INC
  • EP3519070B1 patent drawingFigure 1

AI summary

Polymer-filled ceramic apatites and their uses are provided.