Bioreactor Mature Cell Separation Unit for Continuous Therapy Production

Solution Overview

Problem

Current cell culture growth technologies face inefficiencies and high production losses due to the need for final product filtration at the end of the protocol, which can compromise cell viability and economic viability, especially for cells with a narrow stability window.

Innovation Solution

A bioreactor system with a cell-media recirculation loop and a mature cell separation unit that autonomously monitors and separates mature cells from immature cells during the growth process, using sensors and intelligent control for continuous separation and storage, employing methods like filters, cyclonic separation, and microfluidics, and temperature-controlled storage to maintain cell viability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of substance

If cell culture is extracted wholly at the end of the cell growth protocol using filters, then separation of cells from waste is achieved, but production loss increases and bioreactor efficiency decreases

Engineering Contradiction:

Improvecell production lossVSAvoidbioreactor efficiency

Core Design Contradiction:

Loss of substanceVSProductivity

Solution Approach 1:

The system performs preliminary separation of mature cells from the cell culture during the growth protocol, rather than waiting until the end. The separation unit continuously or periodically removes mature cells as they are produced, preventing the need for final filtration that causes production loss and efficiency reduction.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The separation unit operates continuously or periodically throughout the cell growth protocol, maintaining continuous useful action by constantly separating mature cells as they are produced. This continuous operation maximizes bioreactor efficiency and minimizes production loss compared to end-point extraction.

Inventive Principle:

Principle #20Continuity of useful action

2Reliability

If cell culture is held in bioreactor beyond the viability window, then cell maturation is complete, but cell viability decreases

Engineering Contradiction:

Improvecell viabilityVSAvoidproduction efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The system performs preliminary separation of mature cells from the cell culture during the growth protocol, rather than waiting until the end. The separation unit continuously or periodically removes mature cells as they are produced, preventing the need for final filtration that causes production loss and efficiency reduction.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The system uses sensors to monitor cell maturity and viability in real-time, providing feedback to the control system. This feedback enables the system to automatically adjust separation timing and storage conditions to maintain cell viability within the optimal window, preventing both premature removal and excessive holding.

Inventive Principle:

Principle #23Feedback

3Reliability

If manual monitoring and separation of mature cells is performed, then cell viability is maintained, but labor requirements and operational complexity increase

Engineering Contradiction:

Improvecell viabilityVSAvoidsystem automation

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The system uses sensors to monitor cell maturity and viability in real-time, providing feedback to the control system. This feedback enables the system to automatically adjust separation timing and storage conditions to maintain cell viability within the optimal window, preventing both premature removal and excessive holding.

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The system is designed to autonomously monitor cell culture conditions, identify when cells reach maturity, perform separation, and transfer cells to storage without human intervention. The automated control system manages the entire process, reducing operational complexity despite the advanced functionality.

Inventive Principle:

Principle #25Self-service

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 enhances the efficiency of cell-based production by continuously extracting mature cells, reducing product loss, and maintaining cell viability, thereby making cell-based products more economically viable and reducing the negative effects of prolonged culturing conditions.

Implementation Method 1

The mature cell separation unit may be further configured to direct the mature cells to a mature cell storage unit using at least one of filters, cyclonic separation, and microfluidics

Methodology Applied

Scientific EffectCyclonic separation: Cyclone Separation

Implementation Method 2

The storage unit may be a temperature controlled storage unit

Methodology Applied

Scientific EffectTemperature control: Cooling

Data Source

PatentUS20230242864A1In-time storage of manufactured cells for medical cellular therapy grown and differentiated in bioreactors

Publication Date: 2023.08.03 SCIPERIO INC

AI summary

A system includes a bioreactor having an inlet and an outlet, a cell-media recirculation loop between the outlet of the bioreactor and the inlet of the bioreactor, and a mature cell separation unit positioned along the cell-media recirculation loop wherein the mature cell separation unit is configured for performing separation of mature cells from immature cells and direction of the immature cells back to the inlet of the bioreactor. The system may further include a storage unit for storing the mature cells. The mature cell separation unit may be further configured to direct the mature cells to a mature cell storage unit.