Automated High Cell Density Seed Culture System

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Solution Overview

Problem

Current methods for producing high cell density seed cultures for cryo-preservation lack efficiency and reproducibility, often resulting in variable quality due to manual processes and inadequate real-time monitoring of cellular physiological states.

Innovation Solution

An automated system that includes a cell expansion device with sensors for real-time monitoring of physiological parameters and a control unit to manage medium exchange with cryoprotective agents, allowing for precise control of cell growth and cryopreservation conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If manual processes are used for producing HCDC preparations, then flexibility in operation is maintained, but quality reproducibility and efficiency deteriorate

Engineering Contradiction:
Improvequality reproducibilityVSAvoidautomation system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The system enables self-service operation where the automated production system performs medium exchange, monitoring, and preparation steps without manual intervention. The control unit automatically manages the entire HCDC preparation process from cell growth monitoring to cryoprotective agent exchange, eliminating manual operations while ensuring consistent quality reproduction across batches

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system implements continuous feedback loops where sensors monitor physiological parameters of HCDC in real-time, and the control unit adjusts medium exchange timing and cryoprotective agent addition based on this feedback. This closed-loop control ensures optimal preparation conditions are maintained throughout the process, significantly improving quality reproducibility

Inventive Principle:
Principle #23Feedback

2Manufacturing precision

If real-time monitoring of physiological parameters is implemented, then process control precision is improved, but system complexity and cost increase

Engineering Contradiction:
Improveprocess control precisionVSAvoidsensor and control system complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The system replaces manual mechanical monitoring and decision-making with automated electronic sensors and control algorithms. Electronic sensors continuously measure physiological parameters such as cell density, pH, and dissolved oxygen, substituting manual sampling and visual inspection with precise, continuous electronic measurement and automated process control

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

Solution Approach 2:

The control unit serves multiple functions: it processes data from various sensors, determines when medium exchange is needed, controls the exchange process, monitors cryoprotective agent addition, and maintains records. This multi-functional integration reduces overall system complexity by consolidating control tasks into a single intelligent unit

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

3Reliability

If automated medium exchange with cryoprotective agent is performed, then cryopreservation quality is improved, but process complexity increases

Engineering Contradiction:
Improvecryopreservation qualityVSAvoidoperational simplicity
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The system performs preliminary actions by pre-determining the optimal timing for medium exchange and cryoprotective agent addition based on real-time monitoring of physiological parameters. The control unit calculates and executes these actions before manual intervention would be required, ensuring optimal conditions for cryopreservation are achieved without requiring operational expertise

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The control unit acts as an intermediary between the physiological state of the HCDC and the physical actions of medium exchange and cryoprotective agent addition. It translates sensor data into controlled actions, mediating the complex relationship between cell physiology and preservation protocol execution to ensure optimal outcomes

Inventive Principle:
Principle #24Intermediary (Mediator)

4Productivity

If manual medium exchange processes are used, then equipment simplicity is maintained, but contamination risk and time consumption increase

Engineering Contradiction:
Improveproduction efficiencyVSAvoidcontamination risk
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The system extracts the medium exchange function from manual operations and implements it as an automated process controlled by the control unit. This extraction eliminates human contact with the HCDC during medium exchange, removing the source of potential contamination while significantly reducing the time required for this critical process step

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The automated system enables continuous monitoring and continuous or near-continuous medium exchange operations without interruption by manual handling. The process maintains unbroken sterile conditions throughout medium exchange, eliminating the start-stop nature of manual operations and ensuring continuous protection against contamination while maximizing production efficiency

Inventive Principle:
Principle #20Continuity of useful action

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 system enhances the quality and reproducibility of high cell density seed cultures by reducing manual intervention, minimizing contamination risks, and optimizing cell growth conditions, leading to more efficient and cost-effective production.

Implementation Method 1

collecting data by at least temporally monitoring at least one parameter being indicative of the physiological state of the HCDC

Methodology Applied
Scientific EffectCapacitance: Capacitance

Data Source

PatentEP3795672B1System and method for the generation of high cell density seed culture
Publication Date: 2024.11.20 SARTORIUS STEDIM BIOTECH GMBH
  • EP3795672B1 patent drawingFigure 1
  • EP3795672B1 patent drawingFigure 2
  • EP3795672B1 patent drawingFigure 3

AI summary

System for an automated production of high cell density seed culture, HCDC, preparations, for cryo-preservation comprising a cell expansion device for growing a HCDC in a medium inside a device volume of the cell expansion device, at least one sensor for collecting data by at least temporally monitoring at least one parameter being indicative of the physiological state of the HCDC; and a control unit for processing the collected data to determine whether at least one predetermined criterion is fulfilled by the monitored parameter to control, based on whether the at least one predetermined criterion is fulfilled by the monitored parameter, at least a partial exchange of the medium by a cryo-protective agent, CPA.