Expanded Bed Adsorption Lactoferrin Isolation

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Solution Overview

Problem

Current expanded bed adsorption (EBA) technology is inefficient for large-scale commercial isolation of lactoferrin and other milk proteins due to high liquid volumes and the use of sodium hydroxide, which can cause protein denaturation, limiting their use in nutritional compositions like infant formulas.

Innovation Solution

An improved EBA process involving a diafiltration step, citrate addition, and elution with a sodium chloride buffer of varying concentrations to enhance protein binding and reduce denaturation, allowing for efficient isolation of lactoferrin and other milk proteins from mammalian milk sources.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current EBA technology uses high concentration sodium hydroxide (e.g., 200 mM) during elution, then lactoferrin can be eluted from the matrix, but protein denaturation occurs causing irreversible structural changes

Engineering Contradiction:
Improveprotein structural integrityVSAvoidelution effectiveness
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent changes the chemical parameters of the elution buffer by replacing high concentration sodium hydroxide with sodium chloride at optimized concentrations (0.5-2.0 M), thereby maintaining elution effectiveness while preventing protein denaturation and preserving lactoferrin structural integrity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces citrate as an intermediary substance in the elution buffer system. Citrate acts as a mediator that facilitates lactoferrin elution from the cation-exchange matrix while maintaining gentle conditions that preserve protein structure, avoiding the harsh denaturing effects of high concentration NaOH

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If current EBA technology uses large volumes of liquid during processing, then complete elution of lactoferrin can be achieved, but process efficiency and commercial viability are reduced

Engineering Contradiction:
Improveprocess efficiencyVSAvoidliquid volume
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The patent optimizes the ionic strength and composition parameters of the elution buffer using sodium chloride at specific concentrations (0.5-2.0 M), which improves elution efficiency and allows for reduced liquid volumes while maintaining complete lactoferrin recovery, thereby enhancing process productivity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies a concentrated elution buffer with optimized sodium chloride concentration that achieves complete elution in a single step with reduced volume, rather than using large volumes of dilute buffer, thus improving process efficiency and commercial viability

Inventive Principle:
Principle #16Partial or excessive action

3Ease of manufacture

If conventional purification methods are used to obtain bovine lactoferrin, then lactoferrin can be isolated, but the processes are inefficient for widespread commercial use

Engineering Contradiction:
Improvecommercial scalabilityVSAvoidpurification efficiency
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The patent segments the purification process into distinct stages: (1) cation-exchange EBA for initial concentration and partial purification, (2) optimized elution with sodium chloride-citrate buffer for lactoferrin recovery, and (3) further purification steps if needed. This segmented approach improves both commercial scalability and purification efficiency compared to conventional single-step methods

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent performs preliminary concentration and pre-purification of lactoferrin from bovine whey using cation-exchange EBA before final elution and purification steps. This preliminary action removes bulk contaminants and concentrates the target protein, making subsequent processing more efficient and commercially viable

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 process reduces liquid volume, minimizes protein denaturation, and increases the yield of lactoferrin, making it suitable for commercial production and use in nutritional products.

Implementation Method 1

applying a milk source to the matrix, and eluting the lactoferrin

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Implementation Method 2

The milk source is subjected to a diafiltration process

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Implementation Method 3

adding citrates to the milk source in a concentration ranging from about 0.01 % to about 2.0% w/v of the milk source

Methodology Applied
Scientific EffectChelation:

Data Source

PatentEP3021682B1Expanded bed adsorption methods for isolation of basic milk proteins including lactoferrin
Publication Date: 2019.09.18 MJN US HOLDINGS LLC

AI summary

The present disclosure relates to improved expanded bed adsorption processes for isolating proteins from milk sources. In particular embodiments, the present disclosure provides a process for isolating a milk protein, such as lactoferrin, from a milk source comprising establishing an expanded bed adsorption column comprising a particulate matrix, applying a milk source to the matrix, and eluting the lactoferrin from the matrix with an elution buffer comprising about 0.3 to about 2.0 M sodium chloride.