biochemical engineering

mRNA Vaccine Production

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There aren’t very many positive things to say about a pandemic, but perhaps one positive outcome has been the successful advancement of mRNA vaccine technology. Although some people have the impression that this was very rapidly developed over the past year or so, the mRNA idea dates back to the late 1980s. It’s actually been undergoing development for 20+ years, although obviously the target wasn’t always the coronavirus. As a chemical engineer, I’m interested in the scale-up and production aspects, since that’s what we do best.

As a vaccine production method, the mRNA platform is exciting because it is so fast. Traditional vaccine production methods required the growth of batches of cells to produce the vaccine components. This cell growth is done in big tanks, sort of like beer brewing, but is typically slow. It may take many days or weeks to get one batch done. Some vaccines are still produced in chicken eggs (influenza) or cells grown in small “roller bottles” (measles). All of these are slow and difficult to scale-up to produce billions of doses.

The mRNA production method is not cell-growth based, it just uses a biochemical synthesis method. Here, you just mix a bunch of ingredients, add some enzymes to assemble the mRNA molecules, then enclose them in some nanoparticles. These nanoparticles are a key part of the product, and they serve a couple of key roles: 1) they protect the mRNA from degradation, since RNA is fairly unstable especially once injected into your arm; and 2) they provide the mechanism for the mRNA to get into your muscle cells where your body uses it to produce the “antigen” (the piece of virus protein that your body learns to recognize and fight, if you’re ever infected with the virus in the future).

This biochemical synthesis method can be done in a few hours, versus the days or weeks for the traditional vaccine manufacturing methods. There are still some purification and packaging steps involved which take some more time, but the overall process is still very fast in comparison to the older ones. The mRNA platform is very adaptable too, so the vaccine can be quickly modified if necessary, as the virus mutates, just by changing the “manufacturing template” (DNA plasmid) that assembles the mRNA molecules.

The Sartorius company (a science materials & equipment supplier) has produced a short video giving some information about mRNA vaccines and production, which is pretty good and not too technical.

Chemical Engineering 2021 Student Design Projects

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Photo by fauxels on Pexels.com

Each year, final-year students in Canadian engineering programs pursue open-ended group design projects (“capstone design projects”). This gives them the opportunity to combine the knowledge and skills obtained over the previous 3 academic years (plus work term experience for Waterloo students), and to tackle a problem that is a bit more challenging and wide-ranging than what a typical course assignment can cover.

Our Chemical Engineering class of 2021 has finished up their projects, and some short introductory videos are available for viewing. As usual, the projects are student-selected and they cover a wide range of topics from food processing to low carbon energy systems, reusable plastics to automotive parts manufacturing, and biotechnology to metallurgical processes. Allowing students to pick their own project topic let’s them tailor their experience to an area of interest, that perhaps they want to pursue after graduation.

Anyone interested in chemical engineering, or learning about the wide variety of things that chemical engineers can do, should have a look at some of the videos. They are each only about 1 minute long, give a brief high level overview, and can be found at this link.

Happy Birthday Maud Menten!

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Today (March 20) is the birthday of Canadian Dr. Maud Menten, born in 1879. Who’s that? Anyone who has learned about enzymes and biochemistry (including chemical engineering students) has likely come across the “Michaelis-Menten” equation. This is a way of characterizing how some enzymes work, and a mathematical equation that we can use to measure or predict enzyme kinetics (how fast an enzyme-mediated reaction will occur), which Michaelis and Menten published in 1913.

Maud Menten, pictured here in her youth.
https://www.sciencehistory.org/historical-profile/leonor-michaelis-and-maud-leonora-menten

According to Wikipedia, Maud Menten was born in Port Lambton, Ontario, Canada, which is about 40 km south of Sarnia, on the St. Clair river border between Canada and the U.S. She was one of the first Canadian women to earn a medical doctor degree (at University of Toronto) in 1911. She went to Berlin, Germany, to work with Leonor Michaelis around 1913, who’s team was doing some ground-breaking medical research work in pH, buffers, and enzymes. This collaboration led to the famous publication and Michaelis-Menten equation which is mentioned by students and researchers a myriad of times since.

After some time in Germany, Menten returned to the University of Chicago where she completed a Ph.D. in biochemistry in 1916, studying the effects of adrenalin on hemoglobin. She went on to establish a career on the faculty of the University of Pittsburgh where she continued making significant discoveries in biochemistry and medicine, including early work on electrophoretic separation of proteins (a key biochemistry technique used to this day). After retiring from Pittsburgh, she worked in British Columbia for a few years on cancer research, then returned to Ontario where she passed away in Leamington in 1960.

I frequently ask students if they know who “Menten” was, in the Michaelis-Menten equation, and usually they don’t know. That’s a shame for Canadian students, since she maintained her Canadian citizenship throughout her life, and was a remarkable female scientist at a time when there weren’t very many women accepted, encouraged or active in science.

For more information, Wikipedia is OK, or this article from the Biochemical Society is good.

Microbiome Engineering

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A recent edition of “Chemical Engineering Progress” (a magazine from the American Institute for Chemical Engineers), has an interesting section on “Microbiome Engineering”, as illustrated on the cover. This subject nicely illustrates the diversity of directions that chemical engineers might find in a career path.

A microbiome is essentially a community of various types of microbes that live in an environment. Most of this section discusses the human gut microbiome, those trillions of bacteria that live in our bodies in the digestive tract. Apparently, of all the cells in a human body, about 57% of them are microbial (i.e. bacteria, yeast, etc.), and the rest are human cells.

The microbiome in the gut contains about 3,000 different microbial species. In recent years evidence has been mounting that these microbes play key roles in human nutrition, metabolic diseases (like diabetes), mood disorders, and immune system regulation and disorders. Recent information suggests that people with a poor gut microbiome may be more susceptible to COVID-19 infection and severe complications, for example. There is a lot still to be learned about what constitutes a “good” gut microbiome, and how to manipulate it to improve health.

Of particular interest to chemical engineers is the question of how to manufacture so-called “living biotherapeutic products” (LBPs) that could be implanted or swallowed to modify the gut microbiome and cure diseases. Most pharmaceuticals are either chemicals (single or mixtures) or inactivated (dead) parts of microbes or viruses (as used in vaccines). Producing a living product that can grow and thrive in the gut is a somewhat new challenge, especially if it needs to be a complex mixture of microbes.

Some of these engineering/manufacturing challenges would include issues like:

  • How to shield the manufacturing process and product from oxygen, since many of these gut microbes may be negatively affected by exposure to oxygen (so-called obligate anaerobes).
  • How to get the multiple species of microbes assembled into the LBP. Grow them all separately then mix? Some may grow better in the presence of other species, due to their complex nutritional requirements and symbiotic effects. Growing mixtures of microbes is much more difficult to control if they grow at different rates.
  • How to ensure the final LBP product is consistently the same every time it’s produced. The growth history of microbes can affect their final performance and capabilities, even if they are genetically the same. What we call “process control” in chemical engineering will be crucial to consistency of products.

This area of Living Biotherapeutic Products of quite a new one, although it has certain similarities to existing industrial processes like the production of baker’s yeast or Bifidobacteria for dairy starter cultures. As the medical science evolves and promising new therapeutics are identified, chemical engineers will definitely be involved in translating these developments into manufacturing processes that meet future needs.

The Future of Chemical Engineering

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Sometimes I see people getting concerned about future prospects for chemical engineering careers, usually because of some downturn in the oil and gas markets. I guess we should never stop emphasizing that chemical engineering is much more than oil, gas, and petrochemicals! There is also food, pharmaceuticals, alternative energy, environment, safety, consumer products, plastics, minerals, metals, paper & fibers, etc….

Actually, the next 30 years is probably going to be a very exciting and technically challenging time to be a chemical engineer. The world needs people with the innovation skills to handle new materials and energy processes more than ever. Why is that? Here are a few quick thoughts…

Continue reading →

Handwashing

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With the recent development of a viral pandemic, people are being reminded about the importance of handwashing for infection prevention. Coincidentally, in 2019 my colleague Prof. Marc Aucoin and I supervised a research study on handwashing for the CSA Group, a product standards organization. Specifically, our study aimed to determine if the faucet water flow rate had a significant effect on the ability of handwashing to remove bacteria from the skin.

You can access and read the full report on their website. The bottom line is that no, the water flow rate from the faucet didn’t have a significant effect over the range we tested, from 0.5 to 2.2 gallons per minute (about 2 to 8 litres per minute). Under all of those flow rates, on average about 99.3% of E. coli bacteria would be removed from the hands, which is good to know.

To do this study, we had to control all the other variables as much as possible, including the water temperature, and the amount and type of hand soap used by each person. The other big factor is the way that the hands were washed, including the length of time. For this study, we used a certain protocol from Public Health, and everyone involved in the study learned how to properly wash their hands. This was a good learning opportunity for people, including me, and so I reproduce the protocol that we used below. It’s a useful skill to know how to thoroughly wash your hands these days.

Recommended handwashing technique for infection prevention.