Robots to reshape the biotech industry

Three years ago I was given the opportunity to be part of a unique Ph.D. program in Europe called BacTory, which stands for Bacterial Cell Factories.  This ambitious program was designed as a multi-disciplinary training platform that provides young scientists with scientific and industrial skills for the development of the future microbial-based factories. During three years we have conducted research in biotechnology, attended to technical and innovation courses, and finally carried out an external stay as scientists in a firm.

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Why should we invest in this kind of research initiatives?

Firstly, many of our daily-life products are composed of oil-derived chemicals. Natural reserves of crude oil are expected to decline in the near future, leading to a huge uncertainty in the oil prices and economic instability. Furthermore, the high oil consumption worldwide generates massive amounts of greenhouse gasses that are released into the atmosphere contributing to global warming and harming the environment.

Secondly, there are also natural chemicals produced by plants, which show promising features to replace oil derivatives such as biofuels, natural food additives or medicinal compounds. However, many of these chemicals are too complex to be synthetized by traditional organic chemistry, and on the other hand, plants produce very tiny amounts, which makes direct extraction from feedstocks very unsustainable. For example, the antimalarial drug artemisinin is extracted from the leaves of Artemisia annua plants. Unfortunately, it takes up to eight months to harvest plants for the extraction of the precious compound.

The negative consequences of our strong dependence on oil-derived chemicals and scarcity of natural chemicals urge us to find sustainable alternatives to produce the same commodities. The Bactory program is a response of the Danish scientific community to solve some of these challenges that seriously threat our modern societies.

What are the sustainable alternatives?

A way to replace oil-based chemicals is to find substitutive materials that have the same function from a renewable resource like plants. However, the above-mentioned disadvantages sometimes make this approach unfeasible. In the Bactory program, we have carried out extensive research to develop alternative technologies based on the natural capabilities of living organisms to produce chemicals for humans.

In particular, bacteria are the most simple organisms, which can be easily manipulated and grow very fast in cheap renewable materials. This way we can produce massive amounts of bacteria that secrete or contains the desired product. We take advantage of these features to manipulate genetic information encoded in their DNA or transfer new DNA pieces from other organisms like plants. Remember that genes are DNA fragments that encode for proteins, the tiny machines that make the actual work inside the cell as if it was a small factory. Other genetic elements such as promoters and terminators regulate gene transcription both in space and time. Unfortunately, bacteria usually do not like to have genes or proteins from other organisms. It is important to understand why and find a solution to the problem because these genes are responsible for the production of natural medicines in the plant.

DNA parts
Representation of a DNA backbone (plasmid) containing a gene and other DNA parts

My role in the Bactory program was to manipulate plant genes and proteins with different techniques in order to make them more recognizable by bacterial cells. Luckily I found some tricks that allowed bacteria to accept these genes and ultimately I managed to produce a natural chemical from a plant. These results represent a proof-of-concept but will help other scientists or companies to develop new bacterial strains capable of producing plant medicinal compounds.

Why do we need robots for this if we have Ph.D. students?

One of the challenges that I faced during my project was to test a large number of gene modifications or combinations to identify the most interesting ones. I developed a way to couple the amount of protein produced by bacteria to fluorescence, which can be easily measured. This helped me to reduce the time it takes to find a good gene modification and appropriate cell culture conditions that yielded the maximum amount of protein. However, I just tested a few hundred of conditions because the process of constructing a large number these DNA combinations and testing multiple cell culture conditions without mistakes are major bottlenecks.

To accelerate the construction of a large number of gene or DNA fragment combinations one can order synthetic DNA to a third company. The current automation technologies are capable of synthetizing DNA fragments at a very low cost that will soon be lower than a researcher. In addition to DNA synthesis, liquid handling robots are gradually starting to help humans in time-consuming tasks such as sample preparation or large screenings.  Large firms build sophisticated pipetting robots that can operate 24h 365 days, increasing the high-throughput of the DNA technologies. The problems of these robots are the high cost and steep learning curve to be operated by researchers. Attempts have been made to simplify liquid handling equipment. The major drawback of those systems is that they are task-specific and rather inflexible for multiple applications.

My experience as biotechnologist at Flow Robotics

During the last decade, there have been several events that have revolutionized the field of robotics. The low cost of the 3D printing technology and the increasing number of open source initiatives has also reached this field. Now electronic parts, mechanical designs, open source codes, etc. are freely available giving the opportunity to anyone of learning fast how to build and operate simple robots.

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Example of a 3D printer

Flow Robotics is Start-up Company spun out from the ITU University of Copenhagen that took advantage of this explosion and patented its own robotic platform. Its main advantages are flexibility, the cost-effectiveness of the platform, and a clear goal to make a very simple user interface. These attributes of the Flow Robotics products will put them at the front of the liquid handling applications with the potential to disrupt lab workflows in cell factory development.

The Flow Robotics team is led by a diverse team of a business developer, mechatronic engineers, software engineers and architect designers who provide high-quality standards to the robotic platform.  As part of my visit to Flow Robotics, I assist in the design multiple biotech applications, including cell factory development and act as a consultant. I analyze lab workflows that can be potentially automated and discuss with the Flow Robotic experts the best technological solution to help the final user. I learn about electronics, mechanical components of robots, and software interfaces. Communication between engineers and biotechnologists is not an easy task. However, is one of the most enriching experiences I had during my Ph.D. Flow Robotics and the Bactory program converge as a result of the need for accelerating the development of cell factories, that will ultimately benefit the society. I’m convinced that Flow Robotics will have an impact in this field because we currently don’t have robots with the flexibility level for the research laboratory demands.  

Press releases of the Bactory program and Flow Robotics:

http://healthcaredenmark.dk/news/danish-robot-to-revolutionize-lab-workflows.aspx

http://www.biosustain.dtu.dk/english/Nyhedsbase/Nyhed?id=6C54F061-2F3D-4052-9C63-9ED8819412AC

http://flow-robotics.com/

http://bactory.dnacoil.com/

 

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