Microfluidic Platelet Production Device Using Laminar Flow Shear Stress

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Solution Overview

Problem

Current methods for producing platelets from megakaryocytes are inefficient, with less than 100% production in 6 days and inferior functionality and efficiency compared to turbulent flow-dependent culture methods, and shear stress-dependent microfluidic chip bioreactors fail to achieve high-quality platelet production.

Innovation Solution

A method involving turbulent flow culture of megakaryocytes for at least 6 days followed by exposure to a shear stress-dependent microfluidic chip bioreactor, using a platelet production device with a channel design that captures megakaryocytes and applies laminar flow to promote platelet production, ensuring constant shear stress and efficient platelet release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If megakaryocytes are cultured using shear stress-dependent microfluidic chip bioreactor, then platelet production can be achieved, but the functionality and efficiency are inferior compared to turbulent flow-dependent culture methods

Engineering Contradiction:
Improveplatelet production efficiencyVSAvoidplatelet functionality
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies preliminary action by culturing megakaryocytes under turbulent flow conditions for 6 days before transferring them to the microfluidic chip. This pre-culture phase allows megakaryocytes to mature and develop platelet production capability, ensuring they are in the optimal state for subsequent platelet generation in the chip, thereby improving both efficiency and functionality

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the flow regime parameter from turbulent flow during pre-culture to laminar flow in the microfluidic chip. This parameter change optimizes the culture conditions at different stages: turbulent flow promotes megakaryocyte maturation, while laminar flow with controlled shear stress promotes platelet production, resolving the contradiction between efficiency and functionality

Inventive Principle:
Principle #35Parameter changes

2Productivity

If megakaryocytes are cultured for extended periods to improve maturation, then platelet production efficiency increases, but the culture time and process complexity increase

Engineering Contradiction:
Improveplatelet production efficiencyVSAvoidculture period
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent uses preliminary action by implementing a standardized 6-day turbulent flow pre-culture protocol that optimally matures megakaryocytes before chip transfer. This predetermined culture period has been optimized to achieve maximum platelet production efficiency without excessive time investment, balancing maturation needs with process efficiency

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies dynamics by transitioning megakaryocytes from a turbulent flow environment to a laminar flow microfluidic chip environment. This dynamic change in flow regime allows the system to optimize for different biological functions at different stages, achieving high platelet production efficiency without requiring excessively long culture periods in a single static condition

Inventive Principle:
Principle #15Dynamics

3Productivity

If the channel height is reduced to capture megakaryocytes, then platelet production efficiency improves, but megakaryocyte injection and capture becomes more difficult

Engineering Contradiction:
Improveplatelet production efficiencyVSAvoidmegakaryocyte injection and capture
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent applies local quality by creating a spatial gradient in channel height along the flow direction. The channel height decreases from the injection port toward the collection section, with different sections having different heights optimized for different functions: larger height at injection for easy cell introduction, smaller height downstream for effective platelet capture and production, thus resolving the contradiction between ease of operation and production efficiency

Inventive Principle:
Principle #3Local quality

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 approach enables the efficient production of human platelets with functionality equivalent to those from donated blood, reducing variation in platelet production and improving maturation and functionality.

Implementation Method 1

culturing a megakaryocyte for at least 6 days in a platelet production medium in which a turbulent flow is generated

Methodology Applied
Scientific EffectTurbulent flow: Turbulence

Implementation Method 2

injecting the medium including the megakaryocyte that has undergone step (a) into a platelet production device to expose the megakaryocyte to a laminar flow

Methodology Applied
Scientific EffectLaminar flow: Laminar Flow

Implementation Method 3

expose the megakaryocyte to a laminar flow

Methodology Applied
Scientific EffectShear stress: Shear Stress

Data Source

PatentUS20230147253A1Platelet production method and device
Publication Date: 2023.05.11 KYOTO UNIV
  • US20230147253A1 patent drawing
  • US20230147253A1 patent drawing
  • US20230147253A1 patent drawing

AI summary

The present invention provides a method for producing a platelet comprising: (a) a step of culturing a megakaryocyte for at least 6 days in a platelet production medium in which a turbulent flow is generated; and (b) a step of injecting the medium comprising the megakaryocyte that has undergone step (a) into a predetermined platelet production device to expose the megakaryocyte to a laminar flow.