Ultra-stable Protein Ionic Liquids via Water Extraction

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Solution Overview

Problem

Biological materials like proteins and antibodies are unstable and have short shelf-lives due to the detrimental effects of water, which requires constant refrigeration for storage and handling, but refrigeration is not always feasible, especially in areas without electricity.

Innovation Solution

The development of ultra-stable, water-free protein ionic liquids is achieved by cationizing and anionizing proteins, removing at least 95% of the water, and forming a stable ionic liquid that maintains biological activity and recognition capabilities, allowing for storage and handling at extreme temperatures without refrigeration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If water is present in biological solutions to maintain protein structure and function, then biological activity is preserved, but shelf-life is reduced and refrigeration is required

Engineering Contradiction:
Improvebiological activityVSAvoidshelf-life
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent removes water from the biological solution by converting it into a water-free ionic liquid state. This extraction of the harmful component (water) eliminates the cause of degradation while preserving the protein's biological activity through ionic liquid formation.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent fundamentally changes the physical and chemical parameters of the biological solution by transitioning from an aqueous environment to a water-free ionic liquid state. This parameter change (removing water, adding ionic liquid components) stabilizes the protein structure and extends shelf-life without refrigeration.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If refrigeration is used to preserve biological materials, then stability is improved, but ease of operation is reduced due to infrastructure requirements

Engineering Contradiction:
ImprovestabilityVSAvoidstorage and handling
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent extracts the requirement for refrigeration by removing water from the system. The resulting water-free ionic liquid formulation is inherently stable at ambient temperatures, eliminating the need for cold chain infrastructure and simplifying storage and handling operations.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The ionic liquid formulation provides self-stabilization without external refrigeration. The chemical composition itself (water-free ionic liquid state) inherently prevents degradation, making the system self-sufficient and independent of external cooling infrastructure.

Inventive Principle:
Principle #25Self-service

3Duration of action of stationary object

If water is excluded from antibody preparations to reduce degradation, then shelf-life is increased, but biological activity may be compromised

Engineering Contradiction:
Improveshelf-lifeVSAvoidbiological activity
Core Design Contradiction:
Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent introduces ionic liquid components as intermediaries that replace water's stabilizing functions. These ionic liquid components mediate between the protein structure and the water-free environment, maintaining biological activity while enabling water exclusion for extended shelf-life.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite material system where the protein is integrated with ionic liquid components to form a water-free ionic liquid formulation. This composite structure preserves biological activity while eliminating water, thereby extending shelf-life without compromising functionality.

Inventive Principle:
Principle #40Composite materials

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 resulting protein ionic liquids are stable, resistant to high temperatures, and have significantly longer shelf-lives, eliminating the need for refrigeration and enabling their use in various applications, including diagnostics and therapeutics.

Implementation Method 1

The proteins and/or antibodies are cationized, anionized, and chemically modified into an ionic liquid... removing at least 95% of the water

Methodology Applied
Scientific EffectLyophilization: Freeze Drying

Data Source

PatentUS11274137B1Ultra-stable protein ionic liquids
Publication Date: 2022.03.15 THE GOVERNMENT OF THE UNITED STATES AS REPRESENTED BY THE SECRETARY OF THE AIR FORCE
  • US11274137B1 patent drawing
  • US11274137B1 patent drawing
  • US11274137B1 patent drawing

AI summary

A method comprising: providing aqueous insulin; titrating the aqueous insulin with a mixture of small molecule anions, e.g. D- and L-amino acid esters, small D- and L-peptide pairs, and DL lactate solution, to form an insulin/anion pair solution. Titrating may be performed until the insulin/anion pair solution becomes negative by zeta potential measurement. The insulin/anion pair solution may be dialyzed to remove excess anionic polymer using a membrane sufficient to separate the insulin/anion pairs from excess small molecule anions. The insulin/anion pair solution may be dialyzed or lyophilized to remove all of the water, forming a solid of ultra-stable insulin. The positive electrostatic charge of the aqueous insulin may be confirmed by measuring a positive zeta potential value.