Neutral HMO Purification via Mixed-Bed Ion Exchange

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Solution Overview

Problem

Current methods for purifying human milk oligosaccharides (HMOs) from fermentation broths are technically complex and uneconomical, particularly due to the need for electrodialysis and repetitive ion exchange and adsorption steps, which are not suitable for industrial-scale continuous operation.

Innovation Solution

A process involving the separation of biomass from the fermentation broth using microfiltration and ultrafiltration, followed by treatment with cation-exchange, anion-exchange materials, and a cation-exchange adsorbent resin to obtain a purified solution of neutral HMOs, eliminating the need for electrodialysis and reducing the number of ion exchange and adsorption steps.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional purification methods (electrodialysis and repetitive ion exchange/adsorption) are used, then purity of HMO product is improved, but process complexity and production cost increase significantly

Engineering Contradiction:
Improvepurity of HMO productVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent combines cation-exchange and anion-exchange steps into a single mixed-bed ion-exchange column, where both cationic and anionic resins are packed together. This merging of multiple purification functions into one unit operation achieves the required purity (90% or more) while dramatically reducing process complexity compared to conventional sequential ion exchange and adsorption methods

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The mixed-bed ion-exchange system performs multiple purification functions simultaneously: removing cationic contaminants, anionic contaminants, and colored impurities in a single pass. This multi-functional approach eliminates the need for separate electrodialysis and repetitive adsorption steps, reducing both device complexity and production cost while maintaining high purity

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

2Manufacturing precision

If conventional purification methods are used, then purity of HMO product is improved, but production cost increases

Engineering Contradiction:
Improvepurity of HMO productVSAvoidproduction cost
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

By merging cation-exchange and anion-exchange into a single mixed-bed column operation, the patent reduces the number of unit operations, resin volumes required, and processing time. This consolidation achieves high purity (90% or more) while significantly lowering production cost compared to conventional methods requiring multiple sequential steps including electrodialysis and repetitive adsorption

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The mixed-bed ion-exchange process enables continuous purification operation where the HMO-containing broth continuously passes through the column, and contaminants are continuously removed. This continuous action eliminates the need for batch-wise repetitive ion exchange and adsorption steps, reducing production cost while maintaining high purity

Inventive Principle:
Principle #20Continuity of useful action

3Manufacturing precision

If conventional purification methods are used, then purity of HMO product is improved, but productivity decreases due to multiple repetitive steps

Engineering Contradiction:
Improvepurity of HMO productVSAvoidproduction efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent merges multiple purification steps (cation-exchange, anion-exchange, and adsorption of colored impurities) into a single mixed-bed ion-exchange column operation. This eliminates the need for repetitive sequential steps and electrodialysis, achieving high purity (90% or more) while dramatically improving productivity and production efficiency

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The mixed-bed system enables continuous purification where broth flows continuously through the column and contaminants are removed in a single pass. This continuous operation eliminates downtime between repetitive steps, achieving high purity while maximizing productivity and production efficiency

Inventive Principle:
Principle #20Continuity of useful 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 process achieves a yield of 70% or more and a purity of 90% or more of HMOs, such as 2′-fucosyllactose, without the need for electrodialysis or repetitive ion exchange and adsorption, making it more efficient and cost-effective for industrial-scale production.

Implementation Method 1

treating the crude solution with: a cation-exchange material

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Implementation Method 2

an anion-exchange material

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Implementation Method 3

a cation-exchange adsorbent resin

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS11377462B2Process for the purification of a neutral human milk oligosaccharide (HMO) from microbial fermentation
Publication Date: 2022.07.05 FRIESLANDCAMPINA NEDERLAND BV

AI summary

The invention relates to a process for the purification of a neutral human milk oligosaccharide (HMO) from a fermentation broth, the process comprising the steps of: (i) separating biomass from the fermentation broth to provide a crude solution; (ii) treating the crude solution with: (a) a cation-exchange material; (b) an anion-exchange material; and (c) a cation-exchange adsorbent resin; thereby obtaining a purified solution containing the neutral human milk oligosaccharide. Further, the invention relates to a process for fermentatively producing HMO in a fermentation broth and purifying the HMO from the broth.