Gamma-Stable Dextran Solutions for Blood Separation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Conventional methods for separating red blood cells from whole blood using dextran as an aggregant face challenges due to dextran's instability under gamma irradiation, leading to molecular weight decomposition and ineffective sedimentation performance below 200 kD, which complicates the manufacturing process and increases costs.

Innovation Solution

Development of gamma-stable dextran solutions with initial molecular weights greater than 500 kD and the addition of ascorbic acid or its mineral salts, allowing for direct incorporation into the manufacturing process and maintaining effective red blood cell sedimentation performance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If dextran solution is sterilized by gamma irradiation, then sterilization is achieved, but dextran molecular weight decomposes severely

Engineering Contradiction:
Improvesterilization effectivenessVSAvoiddextran molecular weight stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

Ascorbic acid serves as a protective intermediary substance that absorbs or mitigates the harmful effects of gamma irradiation on dextran molecules. The ascorbic acid is mixed with the dextran solution before sterilization, creating a protective environment that allows the dextran to withstand gamma irradiation without severe molecular weight decomposition.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The ascorbic acid is added to the dextran solution before sterilization to provide pre-protection against the upcoming gamma irradiation stress. This beforehand cushioning prevents the dextran from suffering severe molecular weight decomposition when exposed to gamma rays, allowing effective sterilization while preserving dextran integrity.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

2Ease of manufacture

If dextran molecular weight is reduced below 200 kD, then sterilization becomes easier, but RBC sedimentation performance becomes ineffective

Engineering Contradiction:
Improvesterilization easeVSAvoidRBC sedimentation effectiveness
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

Ascorbic acid acts as a protective intermediary that enables dextran to maintain its high molecular weight (>200 kD) structure during gamma irradiation sterilization. Without ascorbic acid, the dextran would decompose to low molecular weight forms that cannot effectively aggregate RBCs. The ascorbic acid ensures the dextran remains in the effective molecular weight range throughout sterilization.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Stability of the object's composition

If dextran is sterilized separately by autoclaving or filtering, then dextran stability is maintained, but manufacturing complexity and contamination risk increase

Engineering Contradiction:
Improvedextran stabilityVSAvoidmanufacturing process complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The invention merges the sterilization function with the dextran solution itself by adding ascorbic acid as a built-in protective agent. This eliminates the need for separate sterilization steps (autoclaving or filtering) that would otherwise be required to maintain dextran stability. The ascorbic acid-containing dextran solution can be sterilized directly by gamma irradiation in the same manufacturing process stream, reducing complexity and contamination risk.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The ascorbic acid additive provides multiple functions: it protects dextran from gamma irradiation damage, enables direct gamma sterilization of the dextran solution, and maintains dextran molecular weight stability. This multi-functionality consolidates what would otherwise require separate manufacturing steps into a single integrated process.

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

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 gamma-stable dextran solutions enable efficient red blood cell aggregation and sedimentation, facilitating the recovery of a large percentage of total nucleated cells, thereby simplifying the blood separation process and reducing handling errors and costs.

Implementation Method 1

exposure to gamma irradiation at a dose between 20 and 50 kGy

Methodology Applied
Scientific EffectGamma irradiation: Radiation

Implementation Method 2

dextran in water is unstable to gamma irradiation resulting in severe molecular weight decomposition of the dextran

Methodology Applied
Scientific EffectMolecular weight decomposition: Decomposition (biological)

Implementation Method 3

dextran as an aggregant to enhance the sedimentation of red blood cells from whole blood

Methodology Applied
Scientific EffectSedimentation: Sedimentation

Implementation Method 4

RBC aggregation and sedimentation

Methodology Applied
Scientific EffectAggregation: Coagulation

Data Source

PatentEP3132262B1Gamma irradiation stabilized dextran solutions and methods of use
Publication Date: 2017.12.13 GENERAL ELECTRIC CO
  • EP3132262B1 patent drawingFigure 1

AI summary

Provided herein are gamma irradiation stable dextran solutions and kits that increase the efficiency of blood separation by allowing the dextran solution to be sterilized by exposure to gamma radiation and maintain sufficient molecular weight to act as a red blood cell aggregant. The solutions contain 1-10% wt/v dextran of an initial molecular weight greater than 500kD and 2-20 wt% ascorbic acid. A non-toxic enhancer like succinate or citrate can be added. Further provided are methods of use.