Spherical Hydroxyapatite Sorbent Production via Ball Milling and Sintering

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Solution Overview

Problem

Conventional methods for producing hydroxyapatite sorbents for chromatographic separation result in irregular particle shapes and sizes, low mechanical strength, and reduced active sites, limiting their effectiveness and durability during use.

Innovation Solution

A method involving the reaction of calcium hydroxide with phosphoric acid and ammonium phosphate monobasic to form hydroxyapatite particles, followed by milling, dispersant addition, spray-drying, and sintering to produce spherical, porous hydroxyapatite particles with enhanced mechanical strength and binding capacity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If conventional wet synthesis is used to produce hydroxyapatite particles, then the production process is simple, but the particles have irregular shape and size with low mechanical strength

Engineering Contradiction:
Improveproduction process simplicityVSAvoidmechanical strength
Core Design Contradiction:
Ease of manufactureVSStrength

Solution Approach 1:

The patent applies preliminary action by performing high-energy ball milling of calcium hydroxide and phosphoric acid powders before reaction. This pre-processing step creates highly dispersed, fine-powdered reactants with increased surface area and reactivity, which enables the subsequent formation of spherical hydroxyapatite particles with uniform size distribution and enhanced mechanical strength, directly resolving the contradiction between simple production and strong particles

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs parameter changes by controlling the ball milling conditions (energy, time, ball-to-powder ratio) and reaction parameters (temperature, pH, reaction time) to transform the physical and chemical properties of the reactants. These parameter optimizations enable the formation of spherical particles with controlled size distribution and high mechanical strength, overcoming the limitations of conventional wet synthesis

Inventive Principle:
Principle #35Parameter changes

2Strength

If heat treatment is applied to improve mechanical strength, then the mechanical strength increases, but the surface active sites are greatly reduced

Engineering Contradiction:
Improvemechanical strengthVSAvoidsurface active sites
Core Design Contradiction:
StrengthVSQuantity of substance

Solution Approach 1:

The patent applies preliminary action by performing high-energy ball milling of calcium hydroxide and phosphoric acid powders before reaction. This pre-processing step creates highly dispersed, fine-powdered reactants with increased surface area and reactivity, which enables the subsequent formation of spherical hydroxyapatite particles with uniform size distribution and enhanced mechanical strength, directly resolving the contradiction between simple production and strong particles

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs parameter changes by controlling the ball milling conditions (energy, time, ball-to-powder ratio) and reaction parameters (temperature, pH, reaction time) to transform the physical and chemical properties of the reactants. These parameter optimizations enable the formation of spherical particles with controlled size distribution and high mechanical strength, overcoming the limitations of conventional wet synthesis

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If irregular particles are used for chromatographic separation, then the production cost is low, but the particles cannot be packed uniformly or densely in the column

Engineering Contradiction:
Improveproduction costVSAvoidparticle uniformity
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent applies preliminary action by performing high-energy ball milling of calcium hydroxide and phosphoric acid powders before reaction. This pre-processing step creates highly dispersed, fine-powdered reactants with increased surface area and reactivity, which enables the subsequent formation of spherical hydroxyapatite particles with uniform size distribution and enhanced mechanical strength, directly resolving the contradiction between simple production and strong particles

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs parameter changes by controlling the ball milling conditions (energy, time, ball-to-powder ratio) and reaction parameters (temperature, pH, reaction time) to transform the physical and chemical properties of the reactants. These parameter optimizations enable the formation of spherical particles with controlled size distribution and high mechanical strength, overcoming the limitations of conventional wet synthesis

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 produces hydroxyapatite sorbents with high bulk density, improved mechanical stability, and increased surface area, enabling efficient chromatographic separation and purification of biomolecules with reproducible performance and reduced operational costs.

Implementation Method 1

reacting an aqueous suspension comprising calcium hydroxide powder with an aqueous solution comprising phosphoric acid and ammonium phosphate monobasic to form a hydroxyapatite suspension comprising primary particles of hydroxyapatite

Methodology Applied
Scientific EffectChemical precipitation: Precipitation

Implementation Method 2

milling the primary particles of hydroxyapatite in the suspension

Methodology Applied
Scientific EffectMilling: Abrasion

Implementation Method 3

spray-drying the suspension to obtain consolidated secondary particles of hydroxyapatite

Methodology Applied
Scientific EffectSpray-drying: Evaporation

Implementation Method 4

sintering the consolidated secondary particles to obtain sintered hydroxyapatite particles

Methodology Applied
Scientific EffectSintering: Sintering

Data Source

PatentEP3114080B1Methods for producing a hydroxyapatite composition
Publication Date: 2021.08.25 BIO RAD LABORATORIES INC
  • EP3114080B1 patent drawingFigure 1~2
  • EP3114080B1 patent drawingFigure 3A
  • EP3114080B1 patent drawingFigure 3B

AI summary

Highly spherical sorbents of porous hydroxyapatite materials and methods of producing these sorbents are disclosed. The sorbents of the present invention have good mechanical stability and are useful as chromatography media for the separation of biomolecules, such as proteins and nucleic acids.