Alkaline Red Blood Cell Storage Solution for Extended Viability

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Solution Overview

Problem

Current red blood cell storage solutions fail to extend storage duration beyond 6 weeks while maintaining viability and functionality, leading to suboptimal recovery rates and increased hemolysis, which is a limitation in managing blood supply demands, especially during emergencies or in regions with intermittent needs.

Innovation Solution

A novel additive solution composition devoid of sodium chloride, incorporating adenine, dextrose, a non-metabolizable membrane-protectant sugar, and a pH buffering system with sodium bicarbonate and disodium phosphate, maintains a pH range of 8 to 9 to favor glycolysis over 2,3-diphosphoglycerate synthesis, thereby enhancing ATP production and reducing hemolysis, allowing for extended storage up to 8 weeks with improved recovery rates.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If conventional additive solutions (AS-1, AS-3, AS-5) are used for red blood cell storage, then storage duration can be extended to 6 weeks, but storage duration cannot be extended beyond 6 weeks while maintaining viability and functionality

Engineering Contradiction:

Improvestorage durationVSAvoidrecovery rate

Core Design Contradiction:

Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent changes the pH parameter of the storage solution to alkaline range (pH 7.2-8.5), replacing conventional acidic solutions. This parameter change shifts the metabolic equilibrium in red blood cells to favor glycolysis over 2,3-DPG synthesis, thereby extending storage duration while maintaining ATP levels and cell viability beyond 6 weeks

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses a composite buffering system containing multiple components (bicarbonate, phosphate, and other buffers) working together to maintain stable alkaline pH. This composite approach provides superior pH stability compared to single-buffer systems, enabling extended storage while maintaining red blood cell functionality

Inventive Principle:

Principle #40Composite materials

2Productivity

If storage duration is extended, then more blood supply can be managed, but hemolysis increases and membrane integrity deteriorates

Engineering Contradiction:

Improveblood supply management capabilityVSAvoidhemolysis

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by using the alkaline pH environment to prevent apoptotic processes before they can cause significant harm. The buffered alkaline solution counteracts the natural tendency toward cell death during storage, reducing membrane degradation and hemolysis that would otherwise limit extended storage capability

Inventive Principle:

Principle #9Preliminary anti-action

3Reliability

If ATP levels are maintained during storage, then in vivo recovery improves, but storage duration is limited by metabolic depletion

Engineering Contradiction:

Improvein vivo recoveryVSAvoidstorage duration

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent inverts the conventional approach by using alkaline pH instead of acidic pH. This inversion changes the metabolic direction in red blood cells, favoring ATP-generating glycolysis over ATP-consuming 2,3-DPG synthesis, thereby maintaining ATP levels and improving in vivo recovery while enabling extended storage duration

Inventive Principle:

Principle #13The other way round (Inversion)

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 solution enables red blood cells to be stored for longer periods with higher ATP concentrations, reduced hemolysis, and improved membrane integrity, facilitating better in vivo recovery and extended circulation duration, thus addressing the limitations of existing solutions by maintaining therapeutic levels of recoverable red blood cells.

Implementation Method 1

maintains a pH range of 8 to 9 to favor glycolysis over 2,3-diphosphoglycerate synthesis, thereby enhancing ATP production

Methodology Applied

Scientific EffectGlycolysis: Fermentation

Implementation Method 2

incorporating adenine, dextrose, a non-metabolizable membrane-protectant sugar

Methodology Applied

Scientific EffectMembrane protection:

Implementation Method 3

thereby enhancing ATP production and reducing hemolysis

Methodology Applied

Scientific EffectHemolysis reduction:

Data Source

PatentUS9314014B2Compositions and methods for the storage of red blood cells

Publication Date: 2016.04.19 UNIVERSITY OF CINCINNATI

AI summary

The present invention provides an aqueous composition for storage of red blood cells consisting essentially of: adenine; dextrose; at least one non-metabolizable membrane-protectant sugar; and a specifically defined pH buffering system. Also provided are improved methods for preserving red blood cells and methods for increasing the viability, membrane retention, and recoverability while suppressing apoptosis, hemolysis, and post-reinfusion clearance of stored red blood cells which utilize the novel compositions.