Bio Business September/October 2018

CANADA NEWS

NEWSMAKER

Reducing opioid abuse via molecular analysis 6

Lewis Kay highlights new methods to study shape-shifting proteins 12

MOMENTS IN TIME A Canadian nanotech hub is born 16

SEPTEMBER/OCTOBER 2018

Championing the Business of Biotechnology in Canada

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NEWSMAKER: LEWIS KAY

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MOMENTS IN TIME

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BIOMEDICAL SELFIES

A UBC team of chemists discover a means for portable diagnostics using cellphones.

Winner of the 2018 Gerhard Herzberg Canada Gold Medal reflects on almost 30 years in the field.

Championing the Business of Biotechnology in Canada

The early days of harnessing Canada’s nanotech community.

Reprinted with permission: Courtesy of MIT Lincoln Laboratory, Lexington, Massachusetts.

standard CANADA NEWS

NEWSMAKER

Reducing opioid abuse via molecular analysis 6

Lewis Kay highlights new methods to study shape-shifting proteins 12

MOMENTS IN TIME A Canadian nanotech hub is born 16

SEPTEMBER/OCTOBER 2018

David Suzuki The future isn’t in plastics

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Championing the Business of Biotechnology in Canada

From Lab to Fab THE DEFINITIVE SOURCE FOR LAB PRODUCTS, NEWS AND DEVELOPMENTS

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September/October 2018

Integrating plasma treatment into manufacturing

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EDITOR’S NOTE 5 CANADIAN NEWS 6 WORLDWIDE NEWS 7

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University of Waterloo is solving global problems at the atomic level

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SOMETIMES THINKING SMALL IS BIG BUSINESS

BY POPI BOWMAN

The pace of development in nanotechnology is quite literally mindboggling, even more so when we consider how many industries it impacts. The Global Nanotechnology Market Outlook 2018-2024 estimates that the market will grow to exceed US$125 billion, and that’s only five years away; who knows, beyond that short time, what other advancements might accelerate the industry’s growth? But there are also challenges – not only potential environmental, health and safety risks, but also public perception.

The average person associates nanotechnology with the stuff of science fiction (and maybe a few nightmares), but the reality is that nanotechnology is unlocking ideas and solutions for more efficient medical diagnosis and treatments, while revolutionizing research and development in many other fields, including energy production/ storage and pollution mitigation. Its top three applications are electronics, energy and biomedical – respectively – accounting for over 70 per cent of the global nanotechnology market. Many of us are already using nanotechnology on a daily basis; nanomaterial coatings are used to enhance the durability of some fabrics and glass, and some sunscreens include nanoscopic titanium dioxide or zinc oxide.

The automotive industry is exploring nanotech-developed materials such as paint and metals, while – on the other end of the spectrum – a team of researchers from Northwestern University and San Diego State University recently unravelled the mystery of what makes a black widow spider’s web so strong.

Canada has a growing role in this multi-billion-dollar industry, but the University of Toronto deserves special credit for establishing the world’s first undergraduate degree in nanotechnology. Its Centre for Advanced Nanotechnology was formed in 1997, and that same year its research team published one of the first-ever papers on the growth of nanowires, rather than microwires. Now, in little more than 20 years, we’ve advanced to the point of being able to 3D print electronics using silver nanoparticle inks, or create a self-cleaning surface by coating it with mineral nano-crystals with an oxidation reaction stronger than bleach, breaking down organic material into base components. The potential applications of the various discoveries are yet to be fully explored, but in this minuscule world, we seem to have discovered limitless potential.

Those who sit on the sidelines of this scientific realm may have questions and apprehensions about where it can take us, but as we delve into nanotech’s Popi Bowman newest discoveries, I think even a skeptic can’t help being inspired.

MANAGING EDITOR

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Championing the Business of Biotechnology in Canada

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CANADIAN NEWS

UBC RESEARCHERS UNCOVER NEW WAYS TO REDUCE OPIOID ABUSE

New research at the University of British Columbia’s Okanagan campus, Harvard Medical School and the University of Texas is exploring the role nanotechnologies can play in reducing opioid abuse by identifying the most at-risk individuals – those who are physiologically predisposed to be affected by opioids – and helping to develop new therapies and treatments. According to the research, the speed and accuracy of nanotechnologies can result in a more effective approach in drug development and identification, along with better screening of patients who may be vulnerable to addiction. Theoretically, nanotechnologies can enable researchers to improve their understanding of multiple addiction variables at the molecular level.

ANCIENT SUNSCREEN HELPED EARLY BACTERIA OXYGENATE THE PLANET

AI ANALYZES THE INTEGRITY OF METALS

Researchers at the University of Waterloo have found a better way to identify atomic structures, to help improve material selection in the aviation, construction and automotive industries. Devinder Kumar, a PhD candidate in systems design engineering at UWaterloo, collaborated with Berlin’s Fritz Haber Institute to develop a powerful AI model that accurately detects different atomic structures in metallic materials, finding imperfections in the metal that were previously undetectable. They were able to generate about 80,000 images of the different kinds of defects and displacements to produce a very effective AI model to identify various types of crystal structures in practical scenarios. The study was published recently in the journal Nature Communications.

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NEW TECHNOLOGY SUPPORTS RAPID DESIGN AND DEPLOYMENT OF MICROFLUIDIC-BASED PRODUCTS

Micralyne Inc., a Canadian manufacturer of biomedical microelectromechanical systems and sensors, has launched its MicraFluidics™ technology – a line of standardized microfluidic process technologies to support high demand from the biomedical and life-sciences industry for rapid design and deployment of integrated microfluidicbased products such as flow cells, biochips, lab-ona-chip, cell sorters, separation and analysis devices, and high-pressure analytical chips. Considered highly functional and versatile, the technology features a variety of substrate options such as silicon, glass and silicon-on-insulator with design flexibility for multi-level channels, electrode patterning for dielectrophoresis and embedded sensors, and choices of glass or silicon as input and output ports.

Cyanobacteria, Tolypothrix. Photo credit: Matthew Parker, Wikimedia.

A new study by geomicrobiologists at the University of Alberta shows that high amounts of iron and silica particles in ancient seawater contributed to the oxygenation of the planet’s atmosphere. But the early organisms, specifically cyanobacteria which produced the oxygen through photosynthesis, were also very susceptible to the sun’s ultraviolet radiation.

That’s where the iron and silica particles in ancient seawater come in, according to Aleksandra Mloszewska, a former PhD student who conducted this research under the supervision of Kurt Konhauser, professor in the Department of Earth and Atmospheric Sciences, and George Owttrim, professor in the Department of Biological Sciences.

“In effect, the iron-silica particles acted as an ancient ‘sunscreen’ for the cyanobacteria, protecting them from the lethal effects of direct UV exposure,” said Konhauser, the senior author from UAlberta. “This was critical on the early Earth before a sufficiently thick ozone layer was established that could enable marine plankton to spread across the globe, as is the case today.”

The research team used a combination of microbiological, spectroscopic, geochemical and modelling techniques to characterize the effect of UV stress on the cyanobacteria and the degree of radiation through the seawater medium. Their results showed that the presence of high silica and iron concentrations in early sea water allowed for the formation of iron-silica formations that remained suspended in the ocean for extended periods of time.

Researchers explained that the buildup of atmospheric oxygen from cyanobacteria helped in the evolution of oxygen-based respiration and multicellular organisms. But they still don’t know why it took so long for oxygen to accumulate permanently in the atmosphere after the initial evolution of cyanobacteria; they suspect that despite the iron-silica precipitates in the water, UV radiation still would have prevented robust growth in cyanobacteria.

These new findings are helping researchers understand not only how early cyanobacteria were affected by the high level of radiation on the early Earth but also the environmental dynamics that affected the oxygenation history of our atmosphere.

“These findings could also be used as a case study to help us understand the potential for the emergence of life on other planets that are affected by elevated UV radiation levels,” said Mloszewska.

The research was conducted in collaboration with the University of Tuebingen and Yale University and was supported by the National Science and Research Council of Canada, and by the NASA Alternative Earths Astrobiology Institute.

WORLDWIDE NEWS

Downloading data from the Internet to your home computer takes about 25 megabits per second (mbps), depending on the quality of your connection. But what if you were downloading data from the moon’s orbit? At NASA, thanks to a pulsar laser beam developed at MIT’s Lincoln Laboratory, Reprinted with permission: Courtesy of MIT Lincoln Laboratory, Lexington, Massachusetts. they are able to do just that – but at an exponentially greater speed of 622 mbps. Now the same technology, called Lunar Laser Communication Demonstration (LLCD), is being applied to overcome challenges in underwater vehicle communications.

“Both our undersea effort and LLCD take advantage of very narrow laser beams to deliver the necessary energy to the partner terminal for high-rate communication,” said Stephen Conrad, a staff member in the Control and Autonomous Systems Engineering Group who developed the pointing, acquisition, and tracking (PAT) algorithm for LLCD. “In regard to using narrow-beam technology, there is a great deal of similarity between the undersea effort and LLCD.” The challenges lie in the absorption and scattering of laser particles in the ocean, which restrict both the distance the beam can travel and the data signaling rate. To address these problems, the Laboratory is developing narrow-beam optical communications that pinpoint a beam from one underwater vehicle to the receiving terminal of a second one.

Most above-ground autonomous systems rely on the use of GPS for positioning and timing data; however, because GPS signals do not penetrate the surface of water, submerged vehicles must find other means to obtain these important data.

“Underwater vehicles rely on large, costly inertial navigation systems, which combine accelerometer, gyroscope and compass data, as well as other data streams when available, to calculate position,” said research team member Thomas Howe. “The position calculation is noise sensitive and can quickly accumulate errors of hundreds of meters when a vehicle is submerged for significant periods of time.”

The fluctuations in a vehicle’s position can make it difficult for an undersea terminal to locate The challenges lie in the absorption and establish a link with incoming and scattering of laser particles in narrow optical beams. In response, the team implemented the ocean, which restrict both the an acquisition scanning function distance the beam can travel and that is used to quickly translate the data signaling rate. To address the beam over the uncertain these problems, the Laboratory is region so that the companion terminal is able to detect and lock developing narrow-beam optical on to keep the beam centered communications that pinpoint a on the terminal’s acquisition and beam from one underwater vehicle communications detector. Using to the receiving terminal of a this methodology, two vehicles second one. can locate, track and effectively establish a link, despite the independent movement of each vehicle underwater. Once linked, the vehicles could potentially use their established connection to transmit hundreds of gigabytes of data in one session.

KEEPING UP WITH “DANCING” ELECTRONS THROUGH ULTRASHORT, MID-INFRARED PULSES

Ultrashort, intense laser pulses in the mid-infrared region have been generated by four Riken scientists. This achievement promises to open new means to explore the ultrafast dynamics of electrons in materials and enable scientists to excite electron plasmas, effectively creating table-top particle accelerators. The Riken team achieved this by chirping both the pulse to be amplified and the pump pulse. This strategy allowed them to use a commercially available amplification crystal and a widely used pump laser. The pulses at 3.3 micrometers had a relatively high energy, and once compressed, they exhibited a peak power approaching those needed for investigating physical phenomena in high fields.

NEW SYNTHETIC ANTIBODY ENABLES CONTROLLED PROTEIN DEGENERATION FOR BETTER CELL ANALYSIS

A novel synthetic antibody that paves the way for an improved functional analysis of proteins has been developed by scientists at the Technical University of Dresden and the Max Planck Institute for Molecular Cell Biology and Genetics. They combined auxin-dependent “protein knockdown” with a synthetic antibody to observe fluorescent proteins in living cells and rapidly remove them in a controlled manner, making functional analysis much easier. By successfully using it in zebrafish, they demonstrated for the first time that an auxin-mediated protein knockdown can also be implemented in complex vertebrates.

ANTI-CANCER DRUG OFFERS POTENTIAL ALTERNATIVE TO TRANSPLANT FOR PATIENTS WITH LIVER FAILURE

Patients suffering sudden liver failure, brought on by injury or drug abuse, could in the future benefit from a new treatment that prevents he need for organ transplant. The study by scientists at University of Edinburgh MRC Centre for Regenerative Medicine, the Cancer Research UK Beatson Institute in Glasgow, and the University of Bristol, found that liver injury triggers a process called senescence. They discovered that using a class of anti-cancer drugs blocks the spread of this process in mice and the organ was able to regenerate after treatment, preventing death from liver injury.

Clinical trials are being planned.

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ADVANCING UNDERSEA OPTICAL COMMUNICATIONS

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FEATURE STORY

Biomedical Selfies A NEW VISION OF PORTABLE DIAGNOSTICS

BY JANA MANOLAKOS

On the road to extraordinary discoveries, a team of University of British Columbia chemists connected the dots this year, and arrived at what they refer to as “biomedical selfies.”

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ed by Prof. Russ Algar, Canada Research Chair in Biochemical Sensing and Michael Smith Foundation for Health Research Scholar, with financial support from NSERC, the UBC team showed that smartphones can offer a more efficient platform for clinical testing, an approach Algar says could be as simple as taking a “biomedical selfie,” a snapshot of a blood or urine sample, while waiting to be seen at a doctor’s office.

“You have medical equipment that is very expensive and typically located in specialized laboratories or core facilities or hospitals,” says Algar. “People need healthcare all over the place, and so anything we can do to make the tools for healthcare more accessible is going to lower the cost and increase efficiency of healthcare across the country.“ His team of researchers uses quantum dots to interact with smartphones like the Samsung Galaxy or iPhone. While quantum dot technology has captured the public’s interest by revolutionizing the television industry with the brightness and colour purity it brings to the screen, Algar says that the quantum dots his team

Professor Russ Algar

applies are engineered very differently: “We use that same luminescence to analyze biological samples like blood or urine when a picture is taken of it with a smartphone camera.”

About four to 10 nanometres in size, the semiconductor nanocrystals are created by wrapping zinc sulphide around a cadmium selenide core. “From there, we attach biological molecules like peptides, antibodies, fragments of genes, other DNA or RNA,” Algar explains, “and these biomolecules are designed to seek out and bind to other biological molecules or biomarkers of a disease.”

When mixed in a chamber or a more complicated micro-fluidic technology, they’ll react depending on how they have been treated. “They could light up or change colour, or a combination of the two, and that change is then measured using the smartphone camera. The camera takes a picture of the reaction of the light emitted, and then an app on the phone will do that analysis.” Software engineers and computer scientists will be developing a specific app, which is still in the early stages.

So how reliable are the tests? Accuracy rates will depend on the type of sample, biomarker and technology, says Algar. “For one of our proof-of-concept demonstrations, we were able to show that the smartphone gave results that were equally accurate to a standard bench top instrument used in a specialized laboratory setting.”

He says that anything a doctor, clinical laboratory or hospital would test in blood, urine, or derivatives of blood like plasma or serum, could be done in principle on the smartphone platforms that they are developing.

“Of course, getting to the same point of having those tests on the smartphone is going to require a lot of time, but in principle there is no reason that we can’t replace everything done in a specialized lab with smartphonebased technology.”

It becomes even more poignant in Canada, where healthcare in remote communities pales in comparison to that available in larger urban centres. In 2010, the Canadian Institute for Health Information reported that a staggering 58 per cent of patients in Nunavut had to be sent outside the territory for treatment or diagnostics.

Clearly, the financial and social toll of delivering care at great distances is burdening.

“One of the great things about using a smartphone for medical diagnostics is that the information can be collected in one place and analyzed in another.

So someone in a remote community or potentially in the developing world could have a test done by a local medical professional, and then the information from that test We use that same luminescence to analyze biological could go immediately to a big, world-leading medical samples like blood or urine when a picture is taken of centre, and a specialist there it with a smartphone camera. could look at that information – Professor Russ Algar, Canada Research Chair in Biochemical Sensing through the Internet and

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FEATURE STORY

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help with the diagnosis and the treatment,” Algar explains.

“That’s a huge benefit because the patient didn’t have to go anywhere near that big centre.”

This new diagnostic technology has the ability to show early indicators of cancer, kidney, liver, or heart disease.

Outside the human body, it could identify pathogens like E. coli or salmonella in food or water. Other potential applications from a public health and security standpoint include pandemics and bioterrorism.

Most researchers will use standard materials and observe simple colour changes, but Algar’s group and others around the world are taking it further by looking at fluorescence, while showing the distinct advantages of using unique materials.

Commercially there has been a push towards smaller, lower-cost devices. Certain big companies like Abbott have had success in point-of-care diagnostics. “I think the smartphone is really the next evolution of it. But, medical diagnostics companies don’t create smartphones. So it becomes a bit of a black box – how it is going to evolve in the commercial sector once it leaves the research sector.”

Even more recently, lab-on-a-chip technology has miniaturized laboratory functions down to the micro-scale.

Algar is currently engaging with people working on this latest development in microfluidic devices, to get them on board with an integrated unit. The chip can do chemistry and manipulation of different samples and reagents, “but

FEATURE STORY

In 2010, the Canadian Institute for Health Information reported that a staggering

58 per cent of patients in Nunavut had to be sent outside the territory

you still need an equally portable way of reading the result of that chemistry.

So the marriage between the lab-on-a-chip system and a smartphone is what I anticipate will be the pinnacle of this idea of portable biomedical analyses,” says Algar.

It’s still early days for Algar and his team as they grapple to further define the parameters. “Everyone recognizes the benefits of this, but no one really knows how it’s going to evolve commercially right now.” He acknowledges that there are still many unanswered questions. For example, how do you set up this technology to work across the different types of phones? Does it work with one, multiple or all smartphones? How will it be regulated so that when you have a smartphone from one company and a piece of test kit from a different company they are compatible?

“We are doing a lot of proof of concept research showing people that this is viable and that these materials and One of the great things about using a smartphone approaches do have advantages.” for medical diagnostics is that the information can Anything that is health related has a very long process be collected in one place and analyzed in another. of validation, and so right now So someone in a remote community or potentially in the team is in the initial stages of the developing world could have a test done by a local discovery in developing the idea, which they hope will transition medical professional, and then the information from into research-based clinical tests that test could go immediately to a big, world-leading over the next five years – and eventually lead to actual clinical medical centre trials and commercialization – Professor Russ Algar, Canada Research Chair in Biochemical Sensing within the next 10 to 20 years. BB

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for treatment or diagnostics.

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NEWSMAKER

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OF HOCKEY

and science An interview with Lewis Kay, winner of the 2018 Gerhard Herzberg Canada Gold Medal

NEWSMAKER

BY KEREN STEPHENSON PHOTOS: MARTIN LIPMAN/NSERC.

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QA +

f there was a periodic table for hockey, it would include the element of “fun” for biochemist Lewis Kay, winner of the prestigious 2018 Gerhard Herzberg Canada Gold Medal, a peer-awarded prize for excellence and influence in research. The University of Toronto professor and senior scientist in molecular medicine at Toronto’s SickKids Hospital spoke to us about his research, and what science and hockey have in common.

What motivates you in your research?

To have a good time. I mean it sounds strange, but if I give you a hockey analogy, winning teams are teams where the players are having fun, right? They want to get on the ice, to just have fun. If you hold your stick too hard you won’t be able to shoot the puck in the net. It’s the same thing in science – you want to just let your mind carry you forward, and so that’s what I try to do. I think if we’re having fun, we’re going to do some really good work. I can hardly predict what is going to happen in the next 20 years… but the goal is just to keep going and try to go to the highest level possible, and if I can do that then I think I will be successful.

How has the technology impacted research over the years?

For nearly three decades we’ve had a fairly extensive research program focused on increasingly larger bio-molecules. For example, 30 years ago the size of a protein we could study was limited to one that might contain about 100 amino acids. Today, we are able to examine much larger, more complex proteins, potentially containing more than 1,000 amino acids, and how such proteins might interact with other large molecules. We are very interested 30 years ago the size of a protein in developing those technologies to we could study was limited to one address our own research but also to enable others in solving problems in that might contain about 100 amino ways that I could not imagine. acids. Today, we are able to examine

much larger, more complex proteins, potentially containing more than 1,000 amino acids, and how such proteins might interact with other large molecules.

Where do you get your molecule samples?

We make our samples using the tools of molecular biology. Starting from the DNA that codes for the protein, we exploit cellular factories that make our

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Can you elaborate on your work?

We develop and use a technology called Nuclear Magnetic Resonance [NMR] Spectroscopy to study bio-molecules, such as proteins which perform many of the important cellular functions. The methodology that we develop allows us to probe how the form of a protein changes in time and in response to interactions with other molecules, or as a result of mutations. The work has implications for understanding how proteins behave “normally” and in diseased states with, in our case, applications in the areas of neurodegeneration and cancer.

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We have developed ways to focus on molecules changing their shapes to form rare conformations that can be critical both to function and malfunction, and these methods are beginning to emerge in the mainstream as well.

proteins for us, and subsequently we purify them or add them to other molecules to study.

What was the moment like when you realized the potential of your research?

There was a time between 2002 and 2003 when we were working on methods for looking at really big molecules – so-called molecular machines – and we finally figured out how to do it. I knew then that this would have some sort of impact, but it has taken about 15 years for the field to start using the methods on a regular basis. We have also developed ways to focus on molecules changing their shapes to form rare conformations that can be critical both to function and malfunction, and these methods are beginning to emerge in the mainstream as well. You start to do these things, but for many years you’re sort of lonely – of course that’s a good thing too, because it means you are at the head of the pack – but that’s kind of a lonely feeling until others start to pick up and build on those methods.

What attracted you to the field of biophysics?

I really like physics; that was the area I wanted to pursue, and with NMR there is a lot of physics involved.

NEWSMAKER

Your methodologies have impacted the work of various laboratories around the world. How do you feel about that?

It’s true that our methods are used around the world in a number of different biochemistry and biophysics labs by people who apply the NMR techniques to study bio molecules in solution. When people copy you, it validates your work. However, I certainly don’t want to give the impression that anything that I’ve done would even be close to some of the great innovations. But even on a small scale you can derive great satisfaction from knowing that your work is well read and appreciated and respected by your colleagues.

You were recently awarded the prestigious 2018 Gerhard Herzberg Canada Gold Medal. What does this honour mean to you?

It’s certainly nice to get recognized by your peers; I’ve been doing this for almost 30 years. There’s a large number of

really good scientists in Canada in a lot of different areas.

You look at the people who have won the Herzberg over the years – they run the gamut from physicists, to biologists, to chemists – many are exceptional individuals, and to be included in that class is a great feeling. BB

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I studied biochemistry as an undergrad because my father was a professor at the University of Alberta, and I leveraged that to get out of a number of courses I didn’t want to take, regrettably including English.

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MOMENTS IN TIME

2001: Canada steps onto the world stage in nanotechnology

BY JANA MANOLAKOS

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ince physicist Richard Feynman first raised the idea of controlling things on a very small scale in 1959, the world has changed dramatically. The notion of manipulating our physical surroundings at the nanometre level gave rise to a series of discoveries on a scale so small they were dwarfed by the width of a human hair; and yet so colossal, they left massive imprints on the planet.

In 2001, the National Institute for Nanotechnology (NINT) stepped onto that world stage as a collaborative initiative launched by the National Research Council of Canada (NRC), the University of Alberta and the Government of Alberta. At that time, NINT established a unique nanotechnology collaboration hub in a $52.2-million purpose-built facility on the university’s campus in Edmonton, with a mission to support the industry while attracting and developing world-class talent.

This collaborative venture opened new doors to nanotechnology development and advanced the commercialization of breakthrough technologies.

In 2017, the institute became the Nanotechnology Research Centre; although still on the premises of the University of Alberta, the research centre is now a branch of the NRC. Despite the changes, the mission remains on course, working to expand Canadian nanotechnology capacity and fostering breakthrough research. BB

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