“Drawing with a pencil requires drawing each line one by one until the figure is complete. However, a stamp only needs to be pressed once to produce the desired shape.”
Biomanufacturing is the most effective way to sustainably obtain materials, and producing vaccines or other drugs through biomanufacturing is crucial for meeting societal treatment needs and curbing health threats.
However, the willingness to develop biological products does not fully match the capabilities of existing tools on the market. Currently, the efficiency of biomass production methods is low, and to truly achieve the use of alternative resources to produce the biomass needed by humanity, the installed capacity for biomass production should increase by at least hundreds of times.
By continuously upgrading process research and the technological platform for biomanufacturing, the cycle of bioprocess research and production can be greatly shortened, optimizing the biomanufacturing process. The core of rapid research and development is a new type of bioreactor.
A bioreactor refers to any environment or engineering equipment that provides suitable conditions for biochemical reactions. It usually refers to devices that use enzymes or living organisms to simulate biological functions, allowing biochemical reactions to occur outside of cells, and can perform both aerobic and anaerobic reactions during the simulation process. It is a crucial device in applications such as tissue engineering, biochemical engineering, and pharmaceutical production.
Currently, using 3D printing to design complex bioreactors has become one of the effective means to upgrade biomanufacturing platforms.
In academia, research teams from MIT and the Indian Institute of Technology Madras have utilized 3D printing technology to create a reusable and easily adjustable “microfluidic bioreactor”; researchers from the University of Crete have obtained a bioreactor for DNA replication purposes through 3D printing; and researchers from Cornell University have 3D printed a microscopic bioreactor capable of manufacturing synthetic intestines.
In the industry, the pace is somewhat slower. Recently, an Argentine biotechnology company, Stämm Biotech, completed a $17 million Series A financing and announced that the funds would be used to develop its next-generation 3D printed bioreactor, preparing for commercialization.
Plug-and-Play Desktop Bioreactor
Traditional industrial-scale production uses large sterilization tanks as bioreactors, which contain culture media to cultivate a certain type of cells or microorganisms. During production, electric instruments are needed for stirring, coolants are used to maintain the required temperature, and appropriate oxygen is provided to support the growth of cell cultures.
In 2014, Yuyo Llamazares Vegh and Federico D’Alvia Vegh co-founded Stämm Biotech, and the company’s vision has always been to make biomanufacturing simple, scalable, and repeatable. Both founders graduated from Argentina’s top universities and have multidisciplinary backgrounds in microbiology, synthetic biology, nanotechnology, and microfluidics.
With the rapid formation and expansion of the modern biomanufacturing industry, a large-scale biomanufacturing industry is on the horizon. Low production efficiency is the main limitation of “scaling up” in the biotechnology industry, and it is also the problem that Stämm Biotech aims to solve.
As the saying goes, “To do a good job, one must first sharpen their tools.” For the reasons mentioned above, Stämm Biotech is developing a microfluidic-based desktop bioreactor.
Stämm plans to integrate the entire bioreactor into a compact, plug-and-play desktop unit. This bioreactor consists of three microfluidic devices, including Cell line-on-a-chip, Bioreactor-on-a-chip, and The Bubble-Free-Bioreactor.
Bioreactor
Cell line-on-a-chip provides a continuous supply of usable cells to initiate the reaction process; Bioreactor-on-a-chip can calibrate parameters such as culture medium, pH, dissolved oxygen, and cell density in real-time; The Bubble-Free-Bioreactor is a bubble-free microbial reactor printed from porous biological materials.
The bubble-free microbial reactor requires multiple microchannels, which keep cells in a continuous, unidirectional, layered flow state, allowing for perfect mixing between cells, culture media, and gases, always maintaining optimal conditions for constant reproduction.
The complex process of the bubble-free microbial reactor with multiple microchannels requires the use of 3D printing technology for manufacturing. However, there are currently no matching production devices on the market. Considering the demand and self-research capabilities, Stämm Biotech decided to develop their own and successfully launched the Sclereid 3D printer.
The Sclereid 3D printer uses proprietary “brick printing technology,” taking advantage of simultaneously printing millions of points, combining the precision and versatility of laser printers. Sclereid is equipped with a printing volume of 29 liters, capable of printing 590 million pixels of size 6 microns per second, with a pixel count per layer reaching 983 million. It can provide a large surface area without compromising dimensional accuracy.
Example of a bubble-free microbial reactor obtained through 3D printing
At the same time, Stämm has also developed design software Cäster that matches the Sclereid 3D printer.
Cäster allows for the visualization, design, and rendering of large-scale microvascular systems in bioreactors, generating images (at almost any resolution) and sending information to the Sclereid 3D printer for real-time printing or establishing an image library for future printing. The company states that Cäster can simulate a microvascular system with a total volume of 16 million liters, equivalent to the total installed capacity for biopharmaceuticals.
With the Sclereid 3D printer, the company can achieve the “plug-and-play” printing of bioreactors required for cultivating live cells or their components (such as bacteria, enzymes). This way, the desktop bioreactor is completed.
According to the company’s official website, compared to traditional bioreactors, its size has been reduced by 200 times, with a processing capacity between 100 to 400 times, and production efficiency will reach 70 times that of traditional bioreactors. This platform will enable continuous and autonomous production of mammalian cells.
However, currently, compared to most large bioreactors, its operational scale remains relatively small. Stämm’s bioreactor can achieve a yield of about 30 liters, rather than the thousands of liters commonly seen in industrial-scale setups. However, the company claims that its core concept can be scaled up to about 5,000 liters.
Although the technology has potential, Stämm is still in the early stages of commercialization. Stämm Biotech has completed the establishment of biological facilities for microfabrication, cell line development, bioprocess optimization, and pilot-scale certification, and will continue to develop one-stop solutions to make biopharmaceuticals for antibody and cell therapies possible from discovery to commercialization.
Currently, it is collaborating with a European biopharmaceutical company focused on producing biosimilars and states that it has five potential new partners in preparation. The company plans to enter “pilot scale” in 2022.
Further Reading:
“Microfluidic Startup Research”
“Metal Additive Manufacturing (3D Printing) Technology and Market – 2022 Edition”
“3D Electronics and Additive Manufacturing Electronics Technology and Market – 2022 Edition”
“3D Printing Hardware Technology and Market – 2022 Edition”
“3D Printing Composite Materials Technology and Market – 2021 Edition”
