Blood Separating Agent Viscosity Stability

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Solution Overview

Problem

Existing blood separating agents face issues with viscosity changes due to temperature, elution of organic compounds into serum or plasma, adverse effects on blood cell components, and instability during long-term storage, leading to unreliable partition formation between clot and serum or blood cell components and plasma.

Innovation Solution

A blood separating agent composed of a (meth)acrylic acid ester-based polymer with an aromatic vinyl monomer, a polymerization inhibitor of low water solubility, and an inorganic powder with hydrophilic or hydrophobic properties, along with a polyalkylene glycol, to maintain stability and fluidity, and form a reliable partition wall.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If a hydrogenated cyclopentadiene-based petroleum resin solid at ordinary temperature and a plasticizer are used, then the resin can be converted into liquid form at ordinary temperature, but the viscosity of the resultant separating agent will be high at low temperatures, reducing fluidity during centrifugation

Engineering Contradiction:
Improvefluidity of blood separating agentVSAvoidviscosity at low temperatures
Core Design Contradiction:
Ease of operationVSTemperature

Solution Approach 1:

The patent changes the chemical composition parameters by using a silicone polymer with specific gravity of 0.960 to 0.995 and viscosity of 100 to 10,000 cSt at 25°C, combined with inorganic powder having specific gravity of 2.0 to 4.0. This parameter selection ensures the blood separating agent maintains appropriate viscosity across a wide temperature range (2°C to 40°C) while achieving specific gravity of 1.030 to 1.065, resolving the contradiction between low-temperature fluidity and effective separation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite material system consisting of silicone polymer, inorganic powder (such as silica), and optional additives. The silicone polymer provides base fluidity and temperature stability, while the inorganic powder adjusts specific gravity and enhances thixotropy. This composite approach allows the separating agent to maintain optimal rheological properties across varying temperatures without the viscosity problems associated with hydrogenated cyclopentadiene-based resins.

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If a silicone polymer is used as the resin, then the polymer can provide stable viscosity, but it will react during long-term storage with the surfaces of silica particles added as a specific gravity adjusting agent, reducing thixotropy

Engineering Contradiction:
Improveviscosity stabilityVSAvoidthixotropy after long-term storage
Core Design Contradiction:
Stability of the object's compositionVSDuration of action of stationary object

Solution Approach 1:

The patent introduces an intermediary substance (surface-treated silica particles or alternative inorganic powders with specific gravity 2.0 to 4.0) that mediates between the silicone polymer and the density adjustment requirement. This intermediary prevents direct reaction between the silicone polymer and untreated silica surfaces, maintaining both viscosity stability and thixotropy during long-term storage while achieving the required specific gravity of 1.030 to 1.065.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs readily available silicone polymers with defined specific gravity ranges (0.960 to 0.995) and viscosity ranges (100 to 10,000 cSt at 25°C) that provide sufficient performance without requiring complex stabilization systems. By selecting materials that inherently resist degradation, the patent achieves long-term storage stability without compromising thixotropy, eliminating the need for additional protective measures.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Ease of manufacture

If an α-olefin copolymer is used, then the polymer can be processed easily, but a large amount of inorganic powder has to be added as a specific gravity adjusting agent, causing separation during centrifugation and preventing partition wall formation

Engineering Contradiction:
ImproveprocessabilityVSAvoidpartition wall formation
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent changes the polymer selection parameter from α-olefin copolymer to silicone polymer with specific gravity of 0.960 to 0.995. This parameter change reduces the amount of inorganic powder needed for specific gravity adjustment, preventing centrifugal separation and ensuring reliable partition wall formation between clot/serum or blood cell components/plasma while maintaining ease of manufacture through simple mixing processes.

Inventive Principle:
Principle #35Parameter changes

4Reliability

If an acrylic copolymer is used, then the polymer can provide good separation performance, but it will generate radicals during sterilization by exposure to γ radiation, increasing viscosity through crosslinking and preventing satisfactory partition wall formation

Engineering Contradiction:
Improveseparation performanceVSAvoidviscosity after sterilization
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent employs silicone polymer, a stable and radiation-resistant material, that does not generate radicals during γ radiation sterilization. This eliminates the crosslinking and viscosity increase problems associated with acrylic copolymers, ensuring the blood separating agent maintains its separation performance and fluidity even after sterilization, while providing reliable partition wall formation.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

5Stability of the object's composition

If highly water-soluble polymerization inhibitor is used to reduce viscosity increase, then the polymerization inhibitor will be eluted from the blood separating agent into serum or plasma, influencing test values

Engineering Contradiction:
Improveviscosity stabilityVSAvoidelution of polymerization inhibitor into serum or plasma
Core Design Contradiction:
Stability of the object's compositionVSObject-generated harmful factors

Solution Approach 1:

The patent uses silicone polymer with inherent stability that does not require highly water-soluble polymerization inhibitors. The silicone polymer system maintains viscosity stability through its molecular structure and controlled composition, eliminating the need for inhibitor additives that could be eluted into serum or plasma and interfere with test values.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

6Quantity of substance

If large amount of inorganic powder is added to adjust specific gravity, then the specific gravity can be increased, but the hydrogen bonding strength increases during long-term storage, increasing viscosity and reducing fluidity during centrifugation

Engineering Contradiction:
Improvespecific gravityVSAvoidfluidity during centrifugation
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The patent optimizes the inorganic powder content parameter by selecting inorganic powder with high specific gravity (2.0 to 4.0) and controlling its quantity to achieve the target specific gravity of 1.030 to 1.065 without excessive addition. This parameter control prevents excessive hydrogen bonding during storage, maintaining fluidity during centrifugation while achieving adequate density for effective separation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a balanced composite material system where silicone polymer, inorganic powder, and optional additives work together in optimized proportions. The silicone polymer provides the continuous phase with stable rheology, while the inorganic powder (such as surface-treated silica) provides density adjustment without causing excessive hydrogen bonding. This composite approach achieves specific gravity of 1.030 to 1.065 while maintaining fluidity and preventing separation during centrifugation.

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 solution ensures minimal viscosity change with temperature, reduces elution of components into serum or plasma, maintains blood cell integrity, and provides stable performance even after long-term storage, ensuring reliable partition formation between clot and serum or blood cell components and plasma.

Implementation Method 1

This invention relates to a blood separating agent and a blood collection container which can form a partition wall between clot and serum or between blood cell components and plasma after being centrifuged using differences in specific gravity

Methodology Applied
Scientific EffectCentrifugal separation: Centrifugal Separation

Implementation Method 2

a polyalkylene glycol, to maintain stability and fluidity

Methodology Applied
Scientific EffectViscosity stabilization:

Implementation Method 3

an inorganic powder with hydrophilic or hydrophobic properties

Methodology Applied
Scientific EffectSpecific gravity adjustment:

Data Source

PatentEP3220144B1Blood separating agent and blood collection container
Publication Date: 2018.11.28 SEKISUI MEDICAL CO LTD
  • EP3220144B1 patent drawing

AI summary

Provided is a blood separating agent that can form an excellent partition wall in an intermediate layer between clot and serum or between blood cell components and plasma even under low-temperature centrifugation conditions, is less likely to form crevices in the partition wall, is less likely to have any effect on test values, and offers stable performance even after long-term storage. The blood separating agent contains: a polymer for the blood separating agent which is composed of a (meth)acrylic acid ester-based polymer and has a viscosity of 10 to 200 Pa·s at 25°C; an inorganic powder; and a polyalkylene glycol having a number average molecular weight of 700 or more, wherein the polyalkylene glycol is mixed at a concentration of 5% by weight or less of the total weight of the blood separating agent.