Bioreactor with Semipermeable Membrane and Transparent Window

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Solution Overview

Problem

Current bioreactors for cell culture and expansion face limitations such as limited versatility in adjusting culture conditions, insufficient online process monitoring, inability to facilitate closed sterile systems, and noncompliance with Good Manufacturing Practices (GMP) standards, leading to inefficient cell growth and potential contamination.

Innovation Solution

A novel bioreactor design featuring a base with curved surfaces and a transparent window for imaging, a semipermeable membrane for oxygenation while excluding viruses and bacteria, and a Luer interface for connecting external devices, along with a rotatable rack and edge computing processor for real-time monitoring and control of culture conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If a traditional bioreactor design is used, then the structure is simple, but the versatility in adjusting culture conditions is limited and online process monitoring is insufficient

Engineering Contradiction:
Improveversatility in adjusting culture conditionsVSAvoidbioreactor structure complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The bioreactor integrates multiple functions into a single system: the transparent base enables both visual monitoring and imaging analysis, the semipermeable membrane provides both oxygenation and sterilization, and the Luer interface allows connection to multiple external devices (sensors, stirrers, harvesters). This multi-functionality resolves the contradiction by enabling versatile culture condition adjustment without proportionally increasing structural complexity.

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

Solution Approach 2:

The patent combines previously separate functions into integrated components. The base merges imaging, monitoring, and culture functions; the membrane merges gas exchange and sterilization; the connector merges multiple device interfaces. This merging approach increases versatility while controlling overall system complexity.

Inventive Principle:
Principle #5Merging (Combining)

2Measurement precision

If a traditional bioreactor design is used, then the device is simple, but online process monitoring and analysis are insufficient

Engineering Contradiction:
Improveonline process monitoring precisionVSAvoidbioreactor structure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces mechanical sampling and offline analysis with optical imaging and automated image analysis. The transparent base allows non-invasive optical monitoring of cells, while the edge computing processor performs automated image analysis to extract cell morphology, density, and health metrics. This substitution achieves precise online monitoring without adding complex mechanical sensing systems.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The transparent base acts as an intermediary that enables optical access to the culture medium for imaging analysis. The edge computing processor serves as an intermediary between the imaging system and the culture conditions, translating visual data into actionable process control parameters. These intermediaries enable precise monitoring without direct mechanical intervention in the culture system.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If the bioreactor uses a semipermeable membrane for oxygenation, then oxygen supply is improved, but the risk of contamination must be prevented

Engineering Contradiction:
Improveoxygen supply to cellsVSAvoidcontamination risk
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The semipermeable membrane provides localized gas exchange functionality at the liquid-gas interface while maintaining barrier properties against contaminants. The membrane's selective permeability allows oxygen and carbon dioxide to pass through while blocking bacteria and larger particles, creating a local quality distinction that enables both oxygenation and protection simultaneously.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The semipermeable membrane utilizes porous material properties to achieve selective transport. The pore size is engineered to permit gas molecules (oxygen, carbon dioxide) to diffuse through while preventing passage of microorganisms and larger contaminants. This porous structure resolves the contradiction by enabling oxygen supply through the membrane while maintaining sterility.

Inventive Principle:
Principle #31Porous materials

4Reliability

If the bioreactor enables closed sterile system operation, then contamination is prevented, but device complexity increases

Engineering Contradiction:
Improvesterility maintenanceVSAvoidclosed system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The semipermeable membrane serves as a flexible thin film barrier that maintains the closed sterile system. This thin film approach achieves sterility protection without requiring complex rigid sealing systems or multiple components. The membrane's flexibility and selective permeability enable reliable contamination prevention while minimizing the complexity of the closed system architecture.

Inventive Principle:
Principle #30Flexible shells and thin films

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 bioreactor enhances cell yield and proliferation rate, maintains sterility, and complies with GMP standards by enabling online analysis and responsive process control, achieving yields of up to 2*10^8 to 10*10^8 cells per bioreactor, while being compatible with all stages of cell culture and harvesting.

Implementation Method 1

The lid comprises a shaft, column, pole, stick, rod, or stem (hereinafter 'shaft') and a semipermeable membrane such as polytetrafluorethylene (PTFE), attached to the shaft. The semipermeable membrane may be gas-permeable or permeable to oxygen but impermeable to viruses and bacteria.

Methodology Applied
Scientific EffectSemipermeable membrane: Semipermeable Membrane

Implementation Method 2

a window disposed on one of the flat surfaces, the window having a higher degree of transparency compared to other portions of the base, wherein images or videos of cells are captured through the window

Methodology Applied
Scientific EffectLight transmission: Light

Data Source

PatentUS11952564B2Closed cell culturing and harvesting system
Publication Date: 2024.04.09 SHANGHAI LONGEVITY CO LTD
  • US11952564B2 patent drawing
  • US11952564B2 patent drawing
  • US11952564B2 patent drawing

AI summary

A bioreactor includes a base and a lid. The base includes two opposing curved or convoluted surfaces, two opposing flat surfaces, a window disposed on one of the flat surfaces, the window having a higher degree of transparency compared to other portions of the base, wherein images or videos of cells are captured through the window by non-invasive ISM device, and a rounded bottom. The lid is attachable to the base. The lid includes a shaft and a semipermeable membrane attached to the shaft, the semipermeable membrane being permeable to oxygen but impermeable to viruses and bacteria. The PAT-based online analysis directs the adaptive manipulations of bioreactor towards efficient, automated, and GMP-compliant clinical protocols of cell culture.