Literature Review: Development of a Modular Open Source Scalable Bioreactor System for Broad Application

Notes to Reader[edit | edit source]

Zotero Group: Hi-Rel Bioreactor

Background[edit | edit source]

Search Strategy & Terms[edit | edit source]

'''

Key words terms (KWT)

1. "term1" AND "term2"
2. "term1"
3. "term1" OR "term2"

Strategies

1. Searched [site] using KWT1 and KWT3

'''

Way too many, will return later (maybe).

What are [Bio-/Chem-]Reactors?[edit | edit source]

The "What" of the topic.

The goal of this literature review is to find the most used commercial bioreactors in medical laboratories, find the most used functions of commercial laboratory bioreactors in the medical industry, identify the differences between our current open source bioreactor and these commercial bioreactors, and identify what changes should be made to our current design to ensure a fair amount of functionality while maintaining open source accessibility.

Theoretical Framework[edit | edit source]

The "How" of the topic.

Significance and Importance[edit | edit source]

The "Why" of the topic.

Current State of the Art[edit | edit source]

The "When" of the topic. Review current state with an emphasis on the development of the field over time.

Table from "The Role of Laboratory-Scale Bioreactors at the Semi-Continuous and Continuous Microbiological and Biotechnological Processes." (2018)

Denomination	Manufacturer	Working volume, l	Cultivation mode	Stirring mode	Reference
BIOSTAT®Cplus	Sartorius staedium biotech	5, 10, 15, 20, 30	Batch	Rushton turbine, 6 blades	(Fazenda et al. 2010)
BIOSTAT® B	Sartorius staedium biotech	1, 2, 5, 10	Batch, semi-batch	Rushton turbine, 3 blades	(Orr et al. 2009; Zheng et al. 2017)
BIOSTAT® Bplus	Sartorius staedium biotech	1, 2, 5, 10	Batch, semi-batch	Rushton turbine, 2 blades	(Frensing et al. 2013; Timoumi et al. 2017b; Tapia et al. 2017; Timoumi et al. 2017a)
Braun airlift fermentor (BIOSTAT® B-DCU II)	Sartorius staedium biotech	2, 5	Batch, semi-batch	Rushton turbine, Airlift	(Orr et al. 2009; Cobas et al. 2016)
New Brunswick FS300 baffled fermenter®	New Brunswick Scientific	3.5, 5, 7.5, 14, 20	Batch, semi-batch	Rushton turbine, 6 blades	(Galvagno et al. 2011)
BioFlo 3000	New Brunswick Scientific	1.6, 3.3, 6.6	Batch, semi-batch	Rushton turbine, 6 blades	(Nitsche et al. 2012)
New Brunswick BioFlo 110 Fermentor	New Brunswick Scientific	1.3, 3, 7.5, 14	Batch, semi-batch	Rushton turbine, 2 blades	(Rioseras et al. 2014)
Multifors	INFORS AG	0.25, 0.5, 0.75, 1	Batch	Rushton turbine, 2 blades	(Jost et al. 2015)
Ralf Plus-System	Bioengineering inc.	2, 3.7, 5, 6.7	Batch, semi-batch	Rushton turbine, 6 blades	(Bellou et al. 2014)
BIOTECH-3BG	Shanghai BaoXing Bio-Engineering Equipment Co., Ltd	3, 5, 7	Batch, semi-batch	Rushton turbine, 6 blades	(Chen et al. 2017a)
Continuous stirred tank reactors (CSTR)	Nano-Mag Technologies Pvt. Ltd	1, 2, 5, 10, 20, 25	Continuous	Rushton turbine, 6 blades	(Zhao et al. 2017)
Ambr®250	Sartorius staedium biotech	0.25	Continuous (cascade-mode)	Rushton turbine, 2 blades	(Moore et al. 2017)

Relevant Stakeholders[edit | edit source]

The "Who" of the topic.

Applicability and Context[edit | edit source]

The "Where" of the Topic

Literature[edit | edit source]

TODO[edit | edit source]

• Do full review on https://pioreactor.com/en-ca
• Fill in all from https://docs.google.com/document/d/101LJigxu7D3VRPI4VEKiX8SMgm8ur7guZIodBO2QvO0/edit?usp=sharing

Existing Open / Maker Bio- Chem- Reactors[edit | edit source]

Open Bioeconomy Lab - Open Source Bioreactor Project[edit | edit source]

Open Source Bioreactor – Open Bioeconomy Lab. (n.d.). Retrieved March 14, 2024, from https://openbioeconomy.org/projects/open-source-bioreactor/

Microbial Bioreactor. (2018). Hackster.Io. Retrieved March 14, 2024, from https://www.hackster.io/open-bioeconomy-lab/microbial-bioreactor-d7f61b

Biomaker/2018-opensourcebioreactor. (2024). [Jupyter Notebook]. Biomaker. https://github.com/Biomaker/2018-opensourcebioreactor (Original work published 2018)

• Objective: Develop a benchtop, batch bioreactor for enzyme and cell-free extract production, focusing on cost reduction and global accessibility.
• Design Goals:
  • Utilize sterile, autoclavable parts.
  • Incorporate temperature, pH, agitation, and media supply control, plus weight and optical density measurement.
  • Embrace a modular structure for flexibility, using open formats and licenses for software/hardware.
  • Ensure components are easily sourced globally, targeting under £500 for a feature-rich version.

Precise, automated control of conditions for high-throughput growth of yeast and bacteria with eVOLVER[edit | edit source]

Wong, B. G., Mancuso, C. P., Kiriakov, S., Bashor, C. J., & Khalil, A. S. (2018). Precise, automated control of conditions for high-throughput growth of yeast and bacteria with eVOLVER. Nature Biotechnology, 36(7), 614–623. https://doi.org/10.1038/nbt.4151

Documentation. (n.d.). FynchBio. Retrieved March 14, 2024, from https://www.fynchbio.com/documentation

• eVOLVER System Overview:
  • A scalable, do-it-yourself (DIY) framework for high-throughput growth experiments with yeast and bacteria.
  • Enables precise, automated control over experimental conditions.
  • Consists of "Smart Sleeves" designed for continuous culture, integrating control over fluidics, optical density, temperature, and stir rate.
• Smart Sleeves Configuration:
  • Accommodate 40 mL autoclavable borosilicate glass vials.
  • Include LED/photodiode sensor pairs for optical density readings, thermistors, and heaters for temperature control, and magnet-attached computer fans to rotate stir bars.
  • Devices can be calibrated for precision and are cost-effective, with individual sleeves costing approximately $25 and requiring about 10 minutes to assemble.
• Fluidic Handling and Multiplexing:
  • Basic fluid handling involves pumps with fixed flow rates and precision actuation.
  • Millifluidic devices enable customized liquid routing for dynamic experiments.
• Applications and Experiments:
  • High-throughput experimental evolution, enabling the study of yeast evolution across multidimensional selection spaces.
  • The ability to maintain culture density selection routines, study genome-scale library fitness under varying selection pressures, and dynamically mix media in continuous culture.
• Research Impact and Advancements:
  • Demonstrates the utility of eVOLVER in enabling complex experimental designs and precise control over experimental conditions, leading to significant advancements in microbial research and biotechnology.

Open-Source bioreactor controller for bacterial protein expression[edit | edit source]

Marinescu, C., & Popescu, R. (2018). Open-Source bioreactor controller for bacterial protein expression. https://doi.org/10.7287/peerj.preprints.27150 ; https://peerj.com/preprints/27150/

• Objective:
  • Design an open-source, cost-effective Arduino-based bioreactor controller for growing microbial cells, demonstrating its functionality with E. coli culture growth, protein expression induction, and harvesting at preset culture densities.
• Key Features:
  • Modular Design: Ensures cost-effectiveness and availability. Includes detailed parts list and schematics for a benchtop stirred tank bioreactor.
  • Functional Prototyping: Demonstrated by successfully maintaining preset parameters, inducing protein expression, and harvesting culture at preset densities. Automatically records process data showing stable parameters and reliable growth curves.
• Implementation Details:
  • Components: Arduino Mega 2560 R3, Ethernet Shield for network access, various modules for temperature, pH, and culture density control.
  • Software: Custom software for controlling microbial growth processes, with features for network access, data logging, and parameter control.
  • Experiments: Utilized for E. coli culture to validate the bioreactor's functionality in laboratory scale experiments.
• Results and Discussion:
  • Confirmed the effectiveness of the controller in managing environmental factors and recording culture parameters.
  • Demonstrated as a flexible, cost-effective alternative to commercial bioreactors, suitable for various scale microbial cultures.

Chi.Bio Reactor[edit | edit source]

Denton, M. C. R., Murphy, N. P., Norton-Baker, B., Lua, M., Steel, H., & Beckham, G. T. (2024). Integration of pH control into Chi.Bio reactors and demonstration with small-scale enzymatic poly(ethylene terephthalate) hydrolysis (p. 2024.03.03.582641). bioRxiv. https://doi.org/10.1101/2024.03.03.582641

Chi.Bio. (n.d.). Retrieved March 14, 2024, from https://chi.bio/

LABmaker. (n.d.). Chi.Bio. LABmaker. Retrieved March 14, 2024, from https://www.labmaker.org/products/chi-bio

• Development and Purpose:
  • Developed as a response to the challenges faced in synthetic biology research.
  • Designed to be user-friendly, addressing widespread demand for its capabilities​​.
• Key Features and Capabilities:
  • Integrates heating, stirring, liquid handling, spectrometry, and optogenetics into a single platform, simplifying laboratory protocols and reducing equipment costs.
  • Features intuitive design and an easy-to-use web interface for quick experiment setup and remote monitoring.
  • Enables experiments to run for weeks without user intervention, with real-time data plotting and dynamic protocol adjustments .
  • Expanded capabilities include continuous pH monitoring and control, allowing for a broader range of biochemical reactions and biological cultivations​​.
• Applications:
  • Characterization and manipulation of biological systems through in situ measurement of multiple orthogonal fluorescent proteins.
  • Maintenance of cells in exponential growth and automated optogenetic feedback regulation of gene expression.
  • Supports long-term laboratory evolution experiments with temporal chemical gradients or UV LED stress .
• Design and Accessibility:
  • Offers a cost-effective solution, significantly lower than commercial bioreactors, making small-scale bioreactors more affordable and accessible.
  • Capable of operating up to the 30 mL scale with features for online optical monitoring, stirring, and temperature control​​.
  • Experimental Setup and Usage:
  • Allows for temperature regulation from ambient up to 55°C, magnetic stirring, and the measurement of culture optical density and fluorescent protein concentrations.
  • Can function as a turbidostat or chemostat, with additional input pumps for dynamic culture variation/chemical induction​​.
• Community and Support:
  • Founded by Harrison Steel, with contributions from Dr. Robert Habgood and Prof. Antonis Papachristodoulou.
  • Supported by a community of users and developers, providing an open-source operating system developed in Python, documentation, and a forum for collaboration​

Space & Extraterrestrial[edit | edit source]

The case for biotech on Mars Nangle, S. N., Wolfson, M. Y., Hartsough, L., Ma, N. J., Mason, C. E., Merighi, M., Nathan, V., Silver, P. A., Simon, M., Swett, J., Thompson, D. B., & Ziesack, M. (2020). The case for biotech on Mars. Nature Biotechnology, 38(4), Article 4. https://doi.org/10.1038/s41587-020-0485-4

• Very good overview of biotechnology in space applications and explicitly outlines need for advanced bioreactor systems that can operate in extraterrestrial environments

Towards Sustainable Horizons: A Comprehensive Blueprint for Mars Colonization

Neukart, F. (2023). Towards Sustainable Horizons: A Comprehensive Blueprint for Mars Colonization (arXiv:2309.16806). arXiv. http://arxiv.org/abs/2309.16806

• Specifically talks about the role of algae bioreactors and gives benefits of using algae bioreactors for mars colonization
• Gives design considerations for bioreactors on mars (again considering algae cultures)
  • Temperature Regulation: Systems to insulate and maintain stable temperatures for algae cultures due to Mars' extreme temperature fluctuations.
  • Radiation Protection: Shielding for algae cultures against cosmic and solar radiation.
  • Optimal Light Source: Use of LEDs to ensure consistent, optimal lighting for photosynthesis, accounting for Mars' distance from the Sun and dust storms.

Use of Photobioreactors in Regenerative Life Support Systems for Human Space Exploration

Fahrion, J., Mastroleo, F., Dussap, C.-G., & Leys, N. (2021). Use of Photobioreactors in Regenerative Life Support Systems for Human Space Exploration. Frontiers in Microbiology, 12, 699525. https://doi.org/10.3389/fmicb.2021.699525

• This paper focussed on reviewing the bioprocess of microbial photosynthesis, specifically using photobioreactors (PBRs) for bioregenerative life support systems (BLSS) in space exploration
  • Further focus onair revitalization which is the efficient removal of CO2 and production of O2 using liquid cultures of photosynthetic microbes in PBRs.
  • Overview of experiments conducted over the last 30 years, highlighting common challenges and similarities.
  • Identification of data gaps and suggestions for future research.
  • Outlines general needs for sustaining life in space.
  • State of the Art: Current technologies and methods for developing BLSS with various techniques and organisms.

Towards a Biomanufactory on Mars

Berliner, A. J., Hilzinger, J. M., Abel, A. J., McNulty, M. J., Makrygiorgos, G., Averesch, N. J. H., Sen Gupta, S., Benvenuti, A., Caddell, D. F., Cestellos-Blanco, S., Doloman, A., Friedline, S., Ho, D., Gu, W., Hill, A., Kusuma, P., Lipsky, I., Mirkovic, M., Luis Meraz, J., … Arkin, A. P. (2021). Towards a Biomanufactory on Mars. Frontiers in Astronomy and Space Sciences, 8. https://www.frontiersin.org/articles/10.3389/fspas.2021.711550

• In Situ Materials Manufacturing (ISM)
  • Necessity increases with mission duration for various objects: cultivation vessels, support structures, plumbing, and tools.
  • Recent advancements indicate ISM's critical role in generating commodities and consumables including plastics, metals, composite-ceramics, and electronics.
  • Plastics identified as high-turnover items; synthetic biology and additive manufacturing proposed for compact, efficient production from basic feedstocks.
  • Microbial bioreactors' versatility allows for direct utilization of Martian CO2, CH4 from Sabatier processes, and waste biomass.
• In Situ Resource Utilization (ISRU)
  • Biomanufacturing on Mars supported by biocatalysts converting local resources into essential products.
  • Martian atmosphere's CO2 and N2, along with water and O2/H2 from electrolysis, crucial for mission sustainability.
  • Emphasizes the need for carbon and nitrogen fixation reactors to produce feedstocks for biomanufacturing.
  • Trace elements/small-usage compounds might be transported from Earth or extracted from Martian regolith; solar energy for bioreactors could vary by location and season.
• Replicability and Sustainability
  • Continuous operation of replicate ISRU bioreactors with backup lines ensures constant supply of chemical feedstocks and biomass.
  • Integration with other biomanufactory elements like anaerobic digestion reactors could achieve near-complete recyclability of materials, minimizing Martian environmental impact.

MELISSA: a loop of interconnected bioreactors to develop life support in Space

Gòdia, F., Albiol, J., Montesinos, J. L., Pérez, J., Creus, N., Cabello, F., Mengual, X., Montras, A., & Lasseur, C. (2002). MELISSA: A loop of interconnected bioreactors to develop life support in Space. Journal of Biotechnology, 99(3), 319–330. https://doi.org/10.1016/S0168-1656(02)00222-5

• MELISSA Loop Development
  • Interconnected continuous bioreactors for space life support.
  • Loop includes four bioreactors and a higher plant compartment.
  • Focus on continuous, controlled operation at pilot scale.
• Advanced Bioreactors in MELISSA
  • Packed-bed reactor for Nitrosomonas and Nitrobacter.
  • Gas-lift photobioreactor for Spirulina platensis culture.
  • Long duration individual and interconnected operation characterized.
• Life Support Functions
  • Atmosphere regeneration, water recycling, waste treatment, and food generation.
  • Importance of regenerative systems for long-distance space missions.
  • Biological systems integration for food generation.
• MELISSA System Components
  • Anaerobic thermophilic fermentation for waste degradation.
  • Anaerobic photosynthetic bacteria for biomass transformation.
  • Nitrogen transformation via Nitrosomonas europaea and Nitrobacter winogradsky.
  • Spirulina platensis and higher plants for O2 production and food.
• System Development and Control
  • Sequential study: individual compartments, then interconnected operation.
  • Pilot plant scale operation focusing on operational stability.
  • Mathematical modeling and control strategies for bioreactor operation.
• Interconnected Operation and Control
  • Continuous operation under control system for steady-state and perturbations.
  • Scale-up based on mathematical models for photobioreactor control.
  • Interconnection experiments demonstrating operational feasibility.

In situ resource utilisation: The potential for space biomining

Gumulya, Y., Zea, L., & Kaksonen, A. H. (2022). In situ resource utilisation: The potential for space biomining. Minerals Engineering, 176, 107288. https://doi.org/10.1016/j.mineng.2021.107288

• Reviews in-situ resources on the Moon, Mars, and Near-Earth Asteroids for space biomining.
• Examines effects of space environment on biomining microbes.
• Discusses space-based bioreactor designs for metal leaching from regoliths.

Theoretical bioreactor design to perform microbial mining activities on mars

Volger, R., Timmer, M. J., Schleppi, J., Haenggi, C. N., Meyer, A. S., Picioreanu, C., Cowley, A., & Lehner, B. A. E. (2020). Theoretical bioreactor design to perform microbial mining activities on mars. Acta Astronautica, 170, 354–364. https://doi.org/10.1016/j.actaastro.2020.01.036

• Gives a bioreactor system design for the integration of bioreactors for microbial mining on Mars, targeting iron extraction from regolith and oxygen/biomass production using Chlorella vulgaris and Shewanella oneidensis.
• Discusses microbial storage: glycerol stock storage at -80°C for reliable microbial inoculation, with emphasis on space cultivability challenges.
• Outlines algae and biomining reactors: Optimization of thin-layer PBRs for algae growth; operational phases include intake, growth, and extraction, focusing on pH balance, nutrient supplementation, and internal airlift mixing suitable for Martian gravity.
• Analyzes nutrient dynamics: Examination of lactate as an electron donor for S. oneidensis and the nutrient interdependency between algae and biomining processes.
• Describes flow and mixing strategy: Validation of an internal airlift reactor design using CFD to ensure homogeneous mixing and particle suspension under Martian conditions.
• Examines regolith utilization for plant growth: Strategies for modifying Martian regolith to reduce toxicity and support plant life, indicating a closed-loop system approach.
• Addresses system sustainability and planetary protection: Proposals for preventing biofilm formation, improving reactor efficiency, and addressing planetary protection concerns.
• Highlights research directions: Underlines the need for further studies on the effects of microgravity, biofilm prevention techniques, and overall system feasibility for extraterrestrial applications.

The smallest space miners: principles of space biomining

Santomartino, R., Zea, L., & Cockell, C. S. (2022). The smallest space miners: Principles of space biomining. Extremophiles, 26(1), 7. https://doi.org/10.1007/s00792-021-01253-w

• Bioreactor Design for Extraterrestrial Conditions: Exploration into bioreactor designs considers the adaptation to low-pressure, Mars-like atmospheres, suggesting potential pathways for supporting life forms such as cyanobacteria in space environments.
• Potential for Biomining Applications: Emerging evidence suggests that with sufficient technological adaptations, the challenges posed by the unique atmospheric composition and pressure of extraterrestrial environments may not significantly limit the feasibility of biomining applications.
• Engineering Considerations for Space Bioreactors: The necessity for low-pressure environments in space biotechnologies has led to innovative engineering approaches, potentially reducing the complexity and requirements for bioreactor designs suitable for use beyond Earth.
• Importance of Temperature Management: Given the critical role of temperature in microbial growth and the unique challenges presented by space environments, the development and use of temperature-controlled bioreactors are emphasized as essential for successful biotechnological applications in space.

A Low-Pressure, N2/CO2 Atmosphere Is Suitable for Cyanobacterium-Based Life-Support Systems on Mars

Verseux, C., Heinicke, C., Ramalho, T. P., Determann, J., Duckhorn, M., Smagin, M., & Avila, M. (2021). A Low-Pressure, N2/CO2 Atmosphere Is Suitable for Cyanobacterium-Based Life-Support Systems on Mars. Frontiers in Microbiology, 12. https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.611798

• Developed a low-pressure photobioreactor, Atmos, to simulate Martian atmospheric conditions for cyanobacterial growth research.
• Studied the growth of Anabaena sp. PCC 7938 in a simulated Mars atmosphere of 96% N2, 4% CO2 at 100 hPa pressure.
• Demonstrated that these conditions support vigorous cyanobacterial growth and that Martian regolith analog (MGS-1) can be used as a nutrient source.
• Showed cyanobacterial biomass could feed secondary consumers, suggesting suitability for closed-loop life-support systems on Mars.

Bioreactor General[edit | edit source]

Bioreactor- Definition, Design, Principle, Parts, Types, Applications, Limitations[edit | edit source]

Magar, S. T. (2023, May 7). Bioreactor- Definition, Design, Principle, Parts, Types, Applications, Limitations. https://microbenotes.com/bioreactor/

• Full description of bioreactor functions and uses.
• Examples of bioreactor sizes to scale and reference.
• Multiple examples of different bioreactors listed and displayed.

Synergy of selective buffering, intermittent pH control and bioreactor configuration on acidogenic volatile fatty acid production from food waste[edit | edit source]

Dahiya, S., & Venkata Mohan, S. (2022). Synergy of selective buffering, intermittent pH control and bioreactor configuration on acidogenic volatile fatty acid production from food waste. Chemosphere, 302, 134755. https://doi.org/10.1016/j.chemosphere.2022.134755

• In-depth analysis and experimental procedure of food waste conversion into fatty acids using bioreactors.
• Specifications of bioreactors and diagrams included.
• Detailed pH analysis including calculations and graphs.

Membrane bioreactor for wastewater treatment: A review[edit | edit source]

Membrane bioreactor for wastewater treatment: A review

• Focuses on utilizing a membrane bioreactor for wastewater sanitation.
• Membrane bioreactors combine biological processes with membrane filtration, offering advantages over traditional technologies like activated sludge.
• Tables include in-depth specifications for this type of bioreactor, along with an advantages and disadvantages table.

Membrane Bioreactors for Produced Water Treatment: A Mini-Review[edit | edit source]

Asante-Sackey, D., Rathilal, S., Tetteh, E. K., & Armah, E. K. (2022). Membrane Bioreactors for Produced Water Treatment: A Mini-Review. Membranes, 12(3), Article 3. https://doi.org/10.3390/membranes12030275

• Focus on the types of materials used to create efficient bioreactors with minimal costs.
• Ceramic, polymeric, composite, and modified membranes are considered for their fouling resistance, stability, and costs.

A critical review on nanomaterials membrane bioreactor (NMs-MBR) for wastewater treatment[edit | edit source]

Pervez, M. N., Balakrishnan, M., Hasan, S. W., Choo, K.-H., Zhao, Y., Cai, Y., Zarra, T., Belgiorno, V., & Naddeo, V. (2020). A critical review on nanomaterials membrane bioreactor (NMs-MBR) for wastewater treatment. Npj Clean Water, 3(1), 1–21. https://doi.org/10.1038/s41545-020-00090-2

• Submerged (SMBRs) and side stream MBRs are two basic classifications of MBRs, offering benefits like smaller footprint, high-quality treated water, and low energy consumption.
• Highlights the advantages of MBRs over other wastewater treatment techniques and their combination with oxidation processes for micropollutant removal.
• Comparison between two widely used bioreactors is included, showcasing efficient options for building a bioreactor.

Bioreactor Usages / Applications[edit | edit source]

The role of laboratory-scale bioreactors at the semi-continuous and continuous microbiological and biotechnological processes[edit | edit source]

Tikhomirova, T. S., Taraskevich, M. S., & Ponomarenko, O. V. (2018). The role of laboratory-scale bioreactors at the semi-continuous and continuous microbiological and biotechnological processes. Applied Microbiology and Biotechnology, 102(17), 7293–7308. https://doi.org/10.1007/s00253-018-9194-z

• Great review, pulled about a dozen references found herein from this
• Contains a table of used medical bioreactors, with one citation each
• Contains a few uses of bioreactor in practice: Penicillin (Penicillium chrysogenum), C. cylindracea ATCC 14830 is the producer of extracellular lipases, CHO cell lines are the producer of monoclonal antibodies, site-specific antibody-drug conjugates, or fusion proteins.

Performance of simultaneous organic and nutrient removal in a pilot scale anaerobic–anoxic–oxic membrane bioreactor system treating municipal wastewater with a high nutrient mass ratio[edit | edit source]

Performance of simultaneous organic and nutrient removal in a pilot scale anaerobic–anoxic–oxic membrane bioreactor system treating municipal wastewater with a high nutrient mass ratio

• Focuses on utilizing a bioreactor system to purify water.
• Several tables displaying specifications and equations.
• Multiple graphs showcasing efficiency.

Role of Bioreactor Technology in Tissue Engineering for Clinical Use and Therapeutic Target Design[edit | edit source]

Selden, C., & Fuller, B. (2018). Role of Bioreactor Technology in Tissue Engineering for Clinical Use and Therapeutic Target Design. Bioengineering, 5(2), 32. https://doi.org/10.3390/bioengineering5020032

• Focuses on the use of bioreactors in medicine and mentions several bioreactor types.
• Important components and mechanical aspects of bioreactors are elaborated.
• Key focus on involving bioreactors in tissue engineering.

Treatment of Oily Wastewater with Membrane Bioreactor Systems[edit | edit source]

Capodici, M., Cosenza, A., Di Trapani, D., Mannina, G., Torregrossa, M., & Viviani, G. (2017). Treatment of Oily Wastewater with Membrane Bioreactor Systems. Water, 9(6), Article 6. https://doi.org/10.3390/w9060412

• Detailed procedure on the cleaning of the bioreactor included, allowing for multiple uses.
• The membrane module cleaning process involves light mechanical cleaning, mechanical agitation, and chemical cleaning with a citric acid solution.

Bioreactor Design[edit | edit source]

Biological wastewater treatment and bioreactor design: a review[edit | edit source]

Narayanan, C. M., & Narayan, V. (2019). Biological wastewater treatment and bioreactor design: A review. Sustainable Environment Research, 29(1), 33. https://doi.org/10.1186/s42834-019-0036-1

• Discusses several methods and equations for the use of bioreactors in water sanitation.
• Anaerobic digestion is described as a slower process, with ideal conditions for methanogenic bacteria being pH = 7.0 and T = 30–35 °C.

Bioreactor Scalability: Laboratory-Scale Bioreactor Design Influences Performance, Ecology, and Community Physiology in Expanded Granular Sludge Bed Bioreactors[edit | edit source]

Connelly, S., Shin, S. G., Dillon, R. J., Ijaz, U. Z., Sloan, W. T., & Collins, G. (2017). Bioreactor Scalability: Laboratory-Scale Bioreactor Design Influences Performance, Ecology, and Community Physiology in Expanded Granular Sludge Bed Bioreactors. Frontiers in Microbiology, 8. https://doi.org/10.3389/fmicb.2017.00664

• The full-scale bioreactor utilized in the study has a working volume of 425 m3 with a geometric diameter-to-height ratio of 7:12.
• Operates semi-continuously at 37°C with an average OLR of 9 g COD/Lreactor.d.
• Includes in-depth specifications on the methods and materials used to create this bioreactor.

A combined computational-fluid-dynamics model and control strategies for perfusion bioreactor systems in tissue engineering[edit | edit source]

Nascu, I., Sebastia-Saez, D., Chen, T., & Du, W. (2021). A combined computational-fluid-dynamics model and control strategies for perfusion bioreactor systems in tissue engineering. IFAC-PapersOnLine, 54(3), 324–329. https://doi.org/10.1016/j.ifacol.2021.08.262

• Bioreactors are described as machines that develop biological and/or biochemical processes under strict control, including temperature, pH, pressure, waste disposal, and nutrient delivery.
• The article focuses on the use of computational methods with a bioreactor for tissue engineering.

Comparison between a single unit bioreactor and an integrated bioreactor for nutrient removal from domestic wastewater[edit | edit source]

Rout, P. R., Dash, R. R., Bhunia, P., Lee, E., & Bae, J. (2021). Comparison between a single unit bioreactor and an integrated bioreactor for nutrient removal from domestic wastewater. Sustainable Energy Technologies and Assessments, 48, 101620. https://doi.org/10.1016/j.seta.2021.101620

• Main focus on comparing types of bioreactors, their specifications, and methods.
• Testing and experimental analysis comparing the efficiency of more than one type of bioreactors.
• Includes detailed bioreactor diagrams.

Synthesis of supermacroporous cryogel for bioreactors continuous starch hydrolysis[edit | edit source]

Guilherme, E. P. X., de Oliveira, J. P., de Carvalho, L. M., Brandi, I. V., Santos, S. H. S., de Carvalho, G. G. P., Cota, J., & Mara Aparecida de Carvalho, B. (2017). Synthesis of supermacroporous cryogel for bioreactors continuous starch hydrolysis. ELECTROPHORESIS, 38(22–23), 2940–2946. https://doi.org/10.1002/elps.201700208

• In this work, a new bioreactor was synthesized using cryogel monoliths as support material for the immobilization of the alpha amylase from A. oryzae. The bioreactor continuously produced maltose from potato starch.

Continuous Influenza Virus Production in Cell Culture Shows a Periodic Accumulation of Defective Interfering Particles[edit | edit source]

Frensing, T., Heldt, F. S., Pflugmacher, A., Behrendt, I., Jordan, I., Flockerzi, D., Genzel, Y., & Reichl, U. (2013). Continuous Influenza Virus Production in Cell Culture Shows a Periodic Accumulation of Defective Interfering Particles. PLOS ONE, 8(9), e72288. https://doi.org/10.1371/journal.pone.0072288

• A two-stage bioreactor setup was designed in which cells were cultivated in a first stirred tank reactor where an almost constant cell concentration was maintained.
  • Cells were then constantly fed to a second bioreactor where virus infection and replication took place.
  • Using this two-stage reactor system, it was possible to continuously produce influenza viruses.
• Even with very low amounts of DIPs in the seed virus and very low rates for de novo DIP generation, defective viruses rapidly accumulate and, therefore, represent a serious challenge for continuous vaccine production.
  • Yet, the continuous replication of influenza virus using a two-stage bioreactor setup is a novel tool to study aspects of viral evolution and the impact of DIPs
• Two small scale stirred tank bioreactors (1 L working volume Biostat B plus, Sartorius) were used.
• The first lab-scale bioreactor was inoculated with AGE1.CR cells and cultivations were carried out at 37uC, pH 7.2 and a stirring speed of 120 rpm with a working volume of 1 L.
  • Aeration was controlled to 40% DO by pulsed aeration with pure oxygen through a microsparger (whole methods section details a medical use of bioreactor and specifics)

Efficient and stable production of Modified Vaccinia Ankara virus in two-stage semi-continuous and in continuous stirred tank cultivation systems[edit | edit source]

Tapia, F., Jordan, I., Genzel, Y., & Reichl, U. (2017). Efficient and stable production of Modified Vaccinia Ankara virus in two-stage semi-continuous and in continuous stirred tank cultivation systems. PLOS ONE, 12(8), e0182553. https://doi.org/10.1371/journal.pone.0182553

• In this work, continuous production of Modified Vaccinia Ankara (MVA) virus was investigated.
• The process was automated in a two-stage continuous system comprising two connected 1 L stirred tank bioreactors.
• A bioreactor system consisting of two 1 L stirred tank bioreactors (Biostat B Plus, Sartorius) was established (similar to Frensing et al. 2013, Fig 1B). The first bioreactor (Cell Bioreactor, CB) was inoculated with AGE1.CR.pIX cells at 1×106 cells/mL and operated at 37˚C, 120 rpm with Rushton impellers, 40% oxygen saturation and 850 mL working volume (wv). Oxygen saturation was controlled using pulsed aeration with pure oxygen. The pH value was not controlled and only monitored during the batch phase to avoid values below 6.9 (Methods Detailed again)
• 37˚C
• oxygen concentration was at 40–50% saturation
• MVA-CR19 virus was added to VB at an moi of 0.05
• The peristaltic pumps used were Ismatec Reglo-Digital MS2/8-160 (Pump 1 and 2, Fig 1B; Cole-Parmer GmbH, Germany), and Watson Marlow 101U/R (Pump 3, Fig 1B; Waston-Marlow Fluid Technology Group, UK).

Tubular Bioreactor for Probing Baculovirus Infection and Protein Production[edit | edit source]

Wu, H.-C., Hu, Y.-C., & Bentley, W. E. (2016). Tubular Bioreactor for Probing Baculovirus Infection and Protein Production. In D. W. Murhammer (Ed.), Baculovirus and Insect Cell Expression Protocols (pp. 461–467). Springer. https://doi.org/10.1007/978-1-4939-3043-2_23

• This chapter describes several alternative bioreactor systems for baculovirus infection. We provide an example alternative system that holds promise to avoid asynchronous distributions in infection time. Namely, we describe a two-stage reactor system consisting of an upstream continuous stirred tank reactor and a downstream tubular reactor with segmented plug fl ow for probing baculovirus infection and production.
• House made two stage continuous bioreactor: Culture room controlled at 27–28 °C., A glass-blown jacketed spinner fl ask (working volume = 200 mL) made in house., One-liter medium bottles with multi-port cap assemblies (Bellco Biotechnology) to serve as medium reservoir and waste jar., Stirrer plate., Water bath., Needles (22-gauge) and syringe (1 mL) for sampling., Rubber stopper (No. 10)., Stirrer assembly (Bellco Biotechnology)., Masterfl ex precision L/S peristaltic pumps (Cole Palmer)., Microprocessor-controlled peristaltic multichannel pump (Watson Marlow, model 505Du) and a 4-channel pump head (model 205BA)., Watson-Marlow silicone tubing (ID = 1.14 mm) and MasterFlex no. 14 tubing (length = 7.6 m, ID = 1.6 mm).

Staying alive! Sensors used for monitoring cell health in bioreactors[edit | edit source]

O’Mara, P., Farrell, A., Bones, J., & Twomey, K. (2018). Staying alive! Sensors used for monitoring cell health in bioreactors. Talanta, 176, 130–139. https://doi.org/10.1016/j.talanta.2017.07.088* A number of advances in sensor technology have been achieved in recent years, a few of these advances and future research will also be discussed in this review.

• a large number of recombinant monoclonal products have been brought to market such as Rituxan, Herceptin and Remicade
• pH is one of the 3 crucial parameters that must be closely monitored and controlled to prevent cell apoptosis from occurring. pH for optimal cell growth is usually about 7.6 for most animal cells but fluctuations do occur during the cell cycle with pH's reaching levels of 7.0 in some cases
• Cell culture media normally contains buffer agents and sodium bicarbonates to keep pH within optimal working parameters.
• Combined with CO2 sparging to reduce pH and base to increase it. It is also noted that optimal pH changes over the course of a bioprocess.
• even a small change of 0.1 pH units from the optimum can have a large impact on cell viability and concentration.
• Considering that tests have shown that a change of as little as 0.15 pH units can result in a reduction of protein expression levels, so it is highly important that these probes are highly accurate [34].
• Dissolved oxygen (dO) is another key parameter that must be closely monitored and optimised in cell production in a bioreactor.
• Temperature monitoring is crucial to ensure optimal cell viability and product yield during bioprocessing. For mammalian cells the optimal temperature for production has been understood for a number of years to be around 37 °C
• However recent studies have shown that lower temperature in the range of 30–35 °C could yield high productions of some protein types.
• over 37 °c caused a great loss in cell viability and cellular production
• Therefore, it is clear that temperature sensors must operate accurately in a range of 30–40 °c as the process temperature will change over time. Due to this small margin these sensors must be pinpoint accurate to avoid loss in cell viability

Effects of dissolved oxygen on fungal morphology and process rheology during fed-batch processing of Ganoderma lucidum[edit | edit source]

Fazenda, M. L., Harvey, L. M., & McNeil, B. (2010). Effects of dissolved oxygen on fungal morphology and process rheology during fed-batch processing of Ganoderma lucidum. 20(4), 844–851.

• The composition of the medium used in all stages was (g/l): glucose 35, yeast extract 5, peptone 5, KH2PO4 1, and MgSO4·7H2O 0.5.
• All fermentations were carried out in fed-batch mode with pulse-feeding of glucose, yeast extract, and peptone every 24 h, or whenever the glucose concentration fell to 5-10 g/l.
• The reactor used was a 15-l (total volume) stainless steel bioreactor (BIOSTAT C.-DCU; B. Braun Biotech International, Switzerland). The pH was kept at 4.0 by automatic addition of titrants (1 M NaOH and 1 M H2SO4).
• The temperature was kept at 30o C throughout the runs and the agitation rate was set at 300 rpm. The culture conditions chosen were based on previous work [7]. 30 degC and 300 rpm Uncontrolled and controlled dissolved oxygen (DO) fed-batch cultures were performed.
• In the DO controlled process, the DO set-point was at 20% air saturation using a cascade control of agitation, airflow rate, and oxygen enrichment.
• The maximum airflow rate used was at 2.0 volume of air per volume of culture per minute (vvm) in both cultures.
• Real-time values of pH, dissolved oxygen, agitation speed, temperature, airflow rate, and oxygen percentage during fermentations were recorded automatically by the bioreactor software, MFCS DA (Sartorius, U.K.)

Application of bioreactor design principles and multivariate analysis for development of cell culture scale down models[edit | edit source]

Tescione, L., Lambropoulos, J., Paranandi, M. R., Makagiansar, H., & Ryll, T. (2015). Application of bioreactor design principles and multivariate analysis for development of cell culture scale down models. Biotechnology and Bioengineering, 112(1), 84–97. https://doi.org/10.1002/bit.25330

• The production process was operated in a 3-L, stirred tank bioreactor (Applikon Biotechnology, Schiedam, Netherlands) as a fed-batch culture in serum-free medium.
• Temperature, pH, and dissolved oxygen were maintained using TruViu RDPD utility tower, TruLogic controllers, and TruBio software (Finesse Solutions, Santa Clara, CA). Temperature was controlled at 35C. pH was controlled at 7.2 (0.1 deadband) through addition of CO2 or 1.0 molal sodium carbonate. Dissolved oxygen was controlled by delivery of air and/or oxygen through a drilled hole sparger or through sintered spargers with a 15 or 50 mm pore size. Antifoam was added as 10 ppm bolus shots to reduce foam accumulation and avoid exhaust filter wetting

Design and implementation of an affordable laboratory-scale bioreactor for the production of microbial natural products[edit | edit source]

Theodore, C. M., Loveridge, S. T., Crews, M. S., Lorig-Roach, N., & Crews, P. (2019). Design and implementation of an affordable laboratory-scale bioreactor for the production of microbial natural products. Engineering Reports, 1(4), e12059. https://doi.org/10.1002/eng2.12059

• To address these challenges a cost effective, laboratory scale bioreactor was designed and implemented. The constructed bioreactor addresses common problems that small or teaching-focused laboratories face when attempting scale up cultures.

Characterization of TAP Ambr 250 disposable bioreactors, as a reliable scale-down model for biologics process development[edit | edit source]

Xu, P., Clark, C., Ryder, T., Sparks, C., Zhou, J., Wang, M., Russell, R., & Scott, C. (2017). Characterization of TAP Ambr 250 disposable bioreactors, as a reliable scale-down model for biologics process development. Biotechnology Progress, 33(2), 478–489. https://doi.org/10.1002/btpr.2417

• The three cell lines were thawed and expanded in proprietary chemically defined medium at 378C with 5% CO2 overlay prior to inoculation in Ambr 250, 5-L, and 250-L bioreactors.
• About 5-L bench-top bioreactors (Sartorius Stedim Biotech) were used in upstream process development. The processes were scaled up in 250-L single-use bioreactors

Active pharmaceutical ingredient (API) chemicals: A critical review of current biotechnological approaches[edit | edit source]

Kumar, V., Bansal, V., Madhavan, A., Kumar, M., Sindhu, R., Awasthi, M. K., Binod, P., & Saran, S. (2022). Active pharmaceutical ingredient (API) chemicals: A critical review of current biotechnological approaches. Bioengineered, 13(2), 4309–4327. https://doi.org/10.1080/21655979.2022.2031412

• The aim of this article was to generate a framework of bio-based economy by an effective utilization of biomass from the perspectives of agriculture for developing potential end biobased products (e.g. pharmaceuticals, active pharmaceutical ingredients). Our discussion is also extended to the conservatory ways of bioenergy along with development of bio-based products and biofuels. This review article further showcased the fundamental principles for producing these by-products.
• table 1 has many chemicals and their production strategy
• also some important APIs

A practical approach in bioreactor scale-up and process transfer using a combination of constant P/V and vvm as the criterion[edit | edit source]

Xu, S., Hoshan, L., Jiang, R., Gupta, B., Brodean, E., O’Neill, K., Seamans, T. C., Bowers, J., & Chen, H. (2017). A practical approach in bioreactor scale-up and process transfer using a combination of constant P/V and vvm as the criterion. Biotechnology Progress, 33(4), 1146–1159. https://doi.org/10.1002/btpr.2489

• The inoculum trains started from vial thaws and were expanded in shake flasks followed by rocking wave bioreactors (WAVE BioreactorTM 20/50, GE Healthcare, Uppsala, Sweden, or BIOSTATVR RM 20/50, Sartorius Stedim, G€ottingen, Germany) with increasing volumes.
• Glass bioreactors (3 L, Sartorius Stedim, Gottingen, Germany) with a single marine impeller were used with a drilled hole sparger (DHS) or a frit sparger. SS bioreactors at 500 L (Sites A and C) or 2,000 L (Sites B and C) with a single DHS were used. SUBs at 200 L and 2,000 L (Xcellerex XDR200 and XDR2000, GE Healthcare, Marlborough, MA) and 500 L (Hyclone 500 L S.U.B., Thermo Fisher Scientific, Logan, UT) (Sites A and D) with a dual sparger system (Frit sparger for O2 and CO2, DHS for air or N2) were used. The tank geometry, sparger design, and impeller configuration varied from one to another (Table 1)

Continuous Production of Ursodeoxycholic Acid by Using Two Cascade Reactors with Co-immobilized Enzymes[edit | edit source]

Zheng, M.-M., Chen, F.-F., Li, H., Li, C.-X., & Xu, J.-H. (2018). Continuous Production of Ursodeoxycholic Acid by Using Two Cascade Reactors with Co-immobilized Enzymes. ChemBioChem, 19(4), 347–353. https://doi.org/10.1002/cbic.201700415

• Ursodeoxycholic acid (UDCA) is an effective drug for the treatment of hepatitis. In this study, 7a-hydroxysteroid dehydrogenase (7a-HSDH) and lactate dehydrogenase (LDH), as well as 7b-hydroxysteroid dehydrogenase (7b-HSDH) and glucose dehydrogenase (GDH), were co-immobilized onto an epoxy-functionalized resin (ES-103) to catalyze the synthesis of UDCA from chenodeoxycholic acid (CDCA).
• two serial packed-bed reactors.

Design of an Undergraduate Laboratory Experiment Utilizing a Stirred-Tank, Jacketed Bioreactor[edit | edit source]

Middleton, B. (2021). Design of an Undergraduate Laboratory Experiment Utilizing a Stirred-Tank, Jacketed Bioreactor. Honors Theses. https://egrove.olemiss.edu/hon_thesis/1813

• TODO

High Loaded Synthetic Hazardous Wastewater Treatment Using Lab-Scale Submerged Ceramic Membrane Bioreactor[edit | edit source]

Rezakazemi, M., Maghami, M., & Mohammadi, T. (2017). High Loaded Synthetic Hazardous Wastewater Treatment Using Lab-Scale Submerged Ceramic Membrane Bioreactor. Periodica Polytechnica Chemical Engineering, 62. https://doi.org/10.3311/PPch.11459

• The setup included an aerated bio-reactor with a working volume of 10 L and a dispensing pump transferring feed from the feed tank to the aerated bioreactor.
• Three ceramic microfilters (ID = 9 mm, OD = 14 mm, Length = 25 cm) were connected to a collector, which was linked to the permeate tank through a plastic tube.
• The permeate tank was vacuumed using a BCV vacuum pump (P 2-S), with vacuum pressure indicated by an analog pressure gauge.
• A pH meter (Lab-215, palintest Inc.) and a dissolved oxygen (DO) probe (HACH, Germany) were installed in the SCMBR for online monitoring of pH and DO.
• The SCMBR operated at a temperature of 32 °C and a steady-state continuous flow rate of 3 mL/min, resulting in a hydraulic retention time (HRT) of 32 hours.
• For drying and avoiding mechanical stress, wet extrudates were placed in an oven at 100 °C for a few hours before being sintered in a furnace (Zohouri Furnace Industries) at 1225 °C for 3 hours with a heating rate of 2 °C/min, producing ceramic tubular membranes.

Process intensification in lactic acid production by three stage membrane integrated hybrid reactor system[edit | edit source]

Pal, P., & Dey, P. (2013). Process intensification in lactic acid production by three stage membrane integrated hybrid reactor system. Chemical Engineering and Processing: Process Intensification, 64, 1–9. https://doi.org/10.1016/j.cep.2012.12.006

• The article includes a detailed diagram of the bioreactor.
• Detailed analyses of the pH levels necessary for the process are provided.

Product Removal Strategy and Fouling Mechanism for Cellulose Hydrolysis in Enzymatic Membrane Reactor[edit | edit source]

Lim, S. Y., & Ghazali, N. F. (2020). Product Removal Strategy and Fouling Mechanism for Cellulose Hydrolysis in Enzymatic Membrane Reactor. Waste and Biomass Valorization, 11(10), 5575–5590. https://doi.org/10.1007/s12649-020-01020-6

• 10 g/L of microcrystalline cellulose was hydrolyzed with cellulase in a 100 ml Scott bottle with 0.05 M citrate buffer at pH 5.0 for 72 hours at 50 °C, stirred at 100 rpm.
• Two product removal strategies for ultrafiltration (UF) were tested: Strategy I involved filtering 50% of the hydrolysate after 4 hours of the hydrolysis reaction to remove reducing sugar from the reactor.
• The literature provides detailed specifications of a bioreactor used for cellulose hydrolysis.

Membrane bioreactors and electrochemical processes for treatment of wastewaters containing heavy metal ions, organics, micropollutants and dyes: Recent developments[edit | edit source]

Giwa, A., Dindi, A., & Kujawa, J. (2019). Membrane bioreactors and electrochemical processes for treatment of wastewaters containing heavy metal ions, organics, micropollutants and dyes: Recent developments. Journal of Hazardous Materials, 370, 172–195. https://doi.org/10.1016/j.jhazmat.2018.06.025

• The literature lists electronic materials used in the bioreactor process.
• Electrode materials used in recent studies include monopolar and bipolar forms of stainless steel, boron-doped diamond, aluminum/copper/magnesium alloy, granular and powdered activated carbon, stainless steel coated with single-walled carbon nanotubes, Al/Fe-impregnated granular activated carbon, air, etc., in configurations such as parallel/rectangular, cylindrical, rotating impeller, and moving particle.

Influence of nanoparticles on filterability of fruit-juice industry wastewater using submerged membrane bioreactor[edit | edit source]

Demirkol, G. T., Dizge, N., Acar, T. O., Salmanli, O. M., & Tufekci, N. (2017). Influence of nanoparticles on filterability of fruit-juice industry wastewater using submerged membrane bioreactor. Water Science and Technology, 76(3), 705–711. https://doi.org/10.2166/wst.2017.255

• This article details an example of bioreactors in the food industry.
• A PES membrane was utilized in the flat membrane modules, and a nano-sized ZnO (5 mg/L) solution was passed through the membrane for 24 hours at 25 ± 1 °C with a flow rate of 30 mL/min.

Osmotic membrane bioreactor (OMBR) technology for wastewater treatment and reclamation: Advances, challenges, and prospects for the future[edit | edit source]

Wang, X., Chang, V. W. C., & Tang, C. Y. (2016). Osmotic membrane bioreactor (OMBR) technology for wastewater treatment and reclamation: Advances, challenges, and prospects for the future. Journal of Membrane Science, 504, 113–132. https://doi.org/10.1016/j.memsci.2016.01.010

• Contains a brief description of bioreactors used in osmosis.
• Includes multiple tables with characteristics.
• Features in-depth diagrams of bioreactors.

Nitrogen removal from wastewater: A comprehensive review of biological nitrogen removal processes, critical operation parameters and bioreactor design[edit | edit source]

Mishra, S., Singh, V., Cheng, L., Hussain, A., & Ormeci, B. (2022). Nitrogen removal from wastewater: A comprehensive review of biological nitrogen removal processes, critical operation parameters and bioreactor design. Journal of Environmental Chemical Engineering, 10(3), 107387. https://doi.org/10.1016/j.jece.2022.107387

• In-depth chemical reaction processes included.
• Schematic bioreactor processes detailed.
• Multiple tables with in-depth bioreactor specifications.
• Bioreactor diagrams with processes.

Woodchip bioreactors as treatment for recirculating aquaculture systems’ wastewater: A cost assessment of nitrogen removal[edit | edit source]

Lepine, C., Christianson, L., Davidson, J., & Summerfelt, S. (2018). Woodchip bioreactors as treatment for recirculating aquaculture systems’ wastewater: A cost assessment of nitrogen removal. Aquacultural Engineering, 83, 85–92. https://doi.org/10.1016/j.aquaeng.2018.09.001

• Multiple calculations and equations related to bioreactor characteristics.
• Bioreactor cost analysis to help display cost.
• Several tables displaying bioreactor specifications.
• Multiple useful sources referenced and used in this article.

Conclusions[edit | edit source]

The below was done previous by a past student and has been cleaned up but needs review.

Typical Control Parameters[edit | edit source]

• Basics:
  • pH
  • Oxygen
  • Temperature control
• Nutrient and Density Management:
  • Regulation of feed substances to support cell growth
  • Monitoring and controlling cell culture density
• Gas Management for pH Balance:
  • Utilization of CO2 in conjunction with buffers to adjust and maintain pH levels
  • N2 gas to mitigate oxygen and CO2 levels, aiding in pH control
• pH Buffering:
  • Use of buffer substances to achieve a narrow pH range

Considerations[edit | edit source]

1. Sterilization Requirements
   • Autoclavable
2. Additional Sensors
   • Foam/level
   • Glucose
   • Optical density
3. Accuracy of control
   • sensor accuracy
   • sensor latency
   • pump flow rates
   • sparger design
4. Single Use vs Multi Use
   • Plastics vs Glass vs Steel

Laboratory Applications for Bioreactor Testing[edit | edit source]

• Cultivation of Cell Cultures:
  • Primarily focusing on CHO (Chinese Hamster Ovary) cell lines for various research and production purposes.
• Protein Production and Yield Testing:
  • Utilization of E. coli or similar organisms for the production and testing of protein yields.
• Phototropic Organism Cultivation:
  • Optional cultivation of phototropic organisms, depending on specific research or production needs.
• Generic Drug Production:
  • Facilitation of the production processes for generic pharmaceuticals.

Potential Drugs for Cultivation in Bioreactors[edit | edit source]

• Ustekinumab Production:
  • Utilizing Sp2/0 murine myeloma cells for the cultivation of Ustekinumab, a monoclonal antibody.
• Infliximab Production:
  • Employing mouse myeloma cells (SP2/0 cells) for the production of Infliximab, another monoclonal antibody used in medical treatments.

Bibliography[edit | edit source]

Insert auto-generated Zotero list at end.