Disposable Bioreactor Virus Inactivation via Induction Heating
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Solution Overview
Problem
The bioprocessing industry faces challenges in inactivating viruses, particularly bacteriophages, in disposable bioreactors, as traditional methods like steam sterilization are not applicable due to the temperature sensitivity of plastic materials, and there is a need for a method to ensure virus-free cell cultivation in single-use bioreactors.
Innovation Solution
A bioreactor apparatus and method that uses an induction heater or other heating methods to heat the culture medium to elevated temperatures (55-95°C) for extended periods, allowing for virus inactivation before or during cell cultivation, and includes a system for controlling temperature and agitation within a single-use bioreactor bag or separate heat exchanger to maintain sterility and efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional steam sterilization is used to inactivate viruses, then virus inactivation is effective, but plastic bioreactor materials are damaged due to high temperature sensitivity
Solution Approach 1:
The system separates the sterilization function from the bioreactor vessel by using a removable sterilizable insert (cage structure with baskets) that can be autoclaved separately. This allows the plastic bioreactor to remain intact while the insert undergoes traditional steam sterilization, resolving the contradiction between effective virus inactivation and material integrity.
Solution Approach 2:
A sterilizable insert acts as an intermediary component between the sterilization process and the plastic bioreactor. This insert can withstand autoclaving temperatures and serves as the medium for delivering sterile materials into the bioreactor without exposing the plastic vessel to damaging high temperatures.
2Object-affected harmful factors
If sterile filtration is used to remove microorganisms, then microorganism removal is effective, but viruses like bacteriophages are not inactivated
Solution Approach 1:
The system combines sterile filtration and autoclaving sterilization methods into a unified approach. The sterilizable insert is autoclaved to ensure complete virus inactivation, while also serving as a sterile barrier during media transfer, thereby merging the advantages of both filtration and thermal sterilization.
Solution Approach 2:
Autoclaving uses saturated steam under pressure to achieve temperatures above 100°C, creating a more intense thermal oxidation environment that effectively inactivates viruses and bacteriophages, unlike standard sterile filtration which only removes microorganisms.
3Reliability
If stainless steel bioreactors are used with steam sterilization, then virus inactivation is achieved, but system cost and complexity increase
Solution Approach 1:
The invention employs disposable plastic bioreactor vessels that eliminate the need for complex reusable stainless steel systems. By using a removable sterilizable insert, the system achieves virus inactivation without requiring expensive, complex stainless steel construction, thereby reducing overall system complexity and cost.
Solution Approach 2:
The sterilizable insert serves multiple functions: it acts as a sterilization barrier, a transfer medium for sterile materials, and a support structure for culture media. This multi-functionality eliminates the need for separate complex sterilization systems, reducing overall system complexity.
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 effectively inactivates viruses, reduces bacteriophage contamination, and allows for streamlined virus-free cell cultivation, adapting to the limitations of single-use technology by ensuring effective heat treatment without damaging sensitive materials, thus enhancing the reliability of microbial fermentations.
Implementation Method 1
A bioreactor apparatus and method that uses an induction heater or other heating methods to heat the culture medium to elevated temperatures (55-95°C) for extended periods, allowing for virus inactivation
Implementation Method 2
Holding the medium at a temperature of 60° C. for a duration of 10-12 hours will reduce the presence of contaminating organisms such as bacteriophages
Implementation Method 3
The system is then capable of cooling and controlling the media within the bioreactor bag to the desired process temperature
Data Source
AI summary
The invention discloses a bioreactor apparatus (1;101;201;301) for cultivation of cells comprising: a) a disposable bioreactor vessel (2) with one or more walls (3,4,5) defining an inner volume (6), at least one port (10) in a wall, wherein the disposable bioreactor vessel is positioned in a rigid support structure (8;108); and b) a heater (9;109;209;309), capable of heating an amount of culture medium to a target temperature in the range of 55-95° C., while the amount of culture medium is being confined in or conveyed to the inner volume.