Publications

Artificial Life on a Chip – Katherine Elvira on Microfluidic Platforms for Drug Discovery

UVic researcher, Dr. Katherine Elvira, learned about drug discovery and microfluidics in the final year of an integrated undergraduate Master’s degree. She became fascinated by the topic. This fascination fueled her desire to run her own lab centered around these topics. She recently filed a provisional patent (application number: 62/968,616) titled “Microfluidic Platforms for Drug Discovery.” This technology shows great promise in providing a microfluidic platform to test pharmaceuticals or cosmetics without animal models. In addition, it will allow for better prediction of the pharmacokinetic pathway in humans in a high throughput capacity. Read the interview below to learn more about Katherine’s journey to lead a research group investigating microfluidics for healthcare and drug discovery and her provisional patent.

  1. How long have you been studying microfluidic techniques? When did you become interested in developing microfluidic devices for the construction of materials such as tissues or organs for preclinical or biomedical applications of pharmaceutical products?

 During the final year of my degree I took a course that was taught by a drug discovery company that described how they developed new drugs, and analyzed the way a drug could act with the human body. I also took an upper level course on microfluidics that I found really interesting. I ended up doing my PhD on microfluidics for automated chemical reactions, but I also did some work on artificial cells. My post-doc really broadened my experience, allowing me to get a lot of experience with different types of microfluidic technologies. What I am really interested in is building artificial life on a chip, and that is what I am now doing now, here at UVic.

  1. In one of your publications it is cited that 30% of drug candidates fail upon testing on animals because they can’t predict drug pharmacokinetics. What is the road block researchers are finding when trying to discover the pharmacokinetic pathway in humans?

 You can’t test drugs on humans until the end of the drug development process and animals aren’t humans! This is the simplest way of thinking about it. There are decades of experience in this area and drug discovery researchers are very good at making correlations, but it just isn’t good enough. We are still looking for better ways. For example, there are people developing computational models, or organs on a chip. There are lots of different takes on the same problem. When you put a drug in human and it doesn’t work, it’s too late, billions of dollars have already been spent. The biggest road block is that we don’t know how a drug will act until the drug, in question, is taken to clinical trails and tested on humans. There needs to be better middle steps for drug testing.

  1. How does your invention address the road blocks found in current state-of-the art methods for testing pharmaceutical drugs?

We just don’t have a strong enough understanding of the interactions between molecules and humans. Even a cell is very complex. Drugs have to pass through the cell membrane, and there are loads of things inside the cell and on the cell membrane that affect this process. When you do cell-based assays it is hard to narrow down how a drug candidate interacts with cells because of this complexity. What I was thinking when I designed this technology was: what if we designed the cell from the bottom up, starting with a cell membrane so you can make it bespoke? We needed better in-vitro tests. When we do in-vitro tests we really want to predict what happens in-vivo. These were the problems I was seeing, and the problem that I am addressing through the development of the microfluidic platform for drug discovery patent.

  1. Are you able to construct a variety of different tissues to use in preclinical or pharmaceutical applications?

 Yes. We are looking at complex intestinal models, and we are also starting to work on Alzheimer’s disease models. We want to optimize this technology for a variety of different tissues and diseases.

5.  Can you describe how your technology is a novel platform for high-throughput screening of pharmaceutical molecules and/or cosmetic products?

 All microfluidic technologies are effectively high-throughput. The way that we built this three-droplet model of artificial cells allows us to parallelize it. A comparable system is Parallel Artificial Membrane Permeability Assay (PAMPA). That is the typical 96 well plate, high-throughput model. We are making our technology a lot more biometric but still are able to do it in high-throughput. This technology shows promise to be able to run 900 assays per hour.

  1. How simple is this technology to use and what are the cost benefits?

Once it is up and running it is really easy to use. We are still optimizing the platform. Ideally, someone would be able to follow simple steps that would be geared to their drug of choice for an easy testing methodology.

  1. What are your next steps for this technology?

We want to miniaturize the detection system. Not all drugs fluoresce. Within the next year or so we want to try and discover how to detect drugs that don’t fluoresce within this platform. We would love to develop this in the lab and then somehow miniaturize it.

In the future, we would also want to integrate our current platform with detection instruments that pharmaceutical companies already have, such as mass spectrometers.

What keeps you inspired?

 I am always curious. Having a research lab is like having a big problem, and having the ability to try different ideas to solve the problem. I also like to think that we will be able to discover something that could make the world better.

  1. How do you relax from a long day in the lab or grant writing?

I like to do yoga and snowboard. Hanging out with friends is relaxing to me, human interaction keeps me going! I also really like to travel.

For more information on this technology or to inquire about collaboration please contact Research Partnerships (RPKM) here

Photo Credit: UVic Photo Services

 

Written by Liz Bueckert.

Strengthening the Development of Novel Ideas Through Industry-Academic Partnerships

The University of Victoria (UVic) is a top research school in Canada, and faculty members have a reputation for conducting innovative research that makes a global impact. An industry-academic partnership is a collaboration between a company and a researcher to optimize a new technology. The partnership can develop two ways: 1) A company may have a new technology that needs validation through lab work and academic expertise. 2) A researcher may need optimization of a technology developed in their lab through industry testing and deployment. These partnerships can be an excellent tool to enhance a company’s research and development (R&D), and discover solutions to hard-hitting issues within a specific industry. Partnerships are a mutually beneficial relationship where both parties come together to create change.

Industry-academic partnerships are facilitated by Research Partnerships and Knowledge Mobilization (RPKM) at UVic. The RPKM houses UVic’s Industry Liaison Officers (ILOs) who are passionate about innovation, help connect and foster industry-academic relationships, manage intellectual property (IP), support start-up companies, and assist with bringing new technologies to commercialization. ILOs strengthen partnerships by bringing their savvy business and IP knowledge to both parties. The first step in beginning an industry-academic partnership is contacting an ILO with a new idea. They can connect you with relevant researchers to develop the innovation or highlight technologies ready for commercialization that offers a solution to common problems within your industry. Partnerships can begin early in the research phase, part way through development when a technology needs to be optimized, or when the technology is ready for licensing.

Protecting the IP of the industry partner and researcher is a critical component of a partnership. This is protected through a Non-Disclosure Agreement (NDA).  An NDA protects technology specific know-how, trade secrets, proprietary information, and protects all non-public information of the technology and business. This agreement is valid for a term agreed upon by both parties. In addition, a Sponsored Research Agreements (SRA) may be signed. The SRA will provide details on budget, deliverables and the IP arrangements that are agreed to by the company and lead researcher.

One of the major benefits of an industry-academic partnership is the opportunity to secure funding. When researchers and industry partners utilize grants, they can fund substantial portions of their projects. The most common type of funding is a leveraged cost sharing model. Here, the research cost is shared by a funding agency and the industry partner, where the ratio depends on factors such as research stage, company size, and type of grant. Depending on the type of grant the industry cost can include in-kind contributions. These contributions include anything that the partner supplies that is not cash, such as access to state of the art equipment and research materials. Below is a breakdown of available funding options for different types and stages of projects.

Early Stage Funding

NSERC Alliance Grant

The Alliance grant supports research that will generate knowledge, benefit the Canadian economy, support public policy, and draw on diverse perspectives. The grant can be awarded to a researcher with at least one industry partner. The role of the partner in this grant is flexible. They must assist in cost sharing and be involved in one of the following roles: active participation in research, utilize research results, or mobilize knowledge to ensure research has an impact. There are two funding options for the alliance grant, both options have variable lengths of 1-5 years with different criteria and funding levels.

Option 1:  for small and large private, public, non-profit companies or government organizations with funding goals between $20,000 and $1 million. Cost sharing depends on the size of the company, where NSERC will fund 50% if the company has over 500 employees or 66% if it has under 500.

Option 2: for public, non-profit, and private companies who can work to make a societal challenge, collaborate in a way to include societal perspectives, and demonstrate how the developed technology can be used by industry specific end-users. This grant offers funding in the range of $30,000 – $100,000 in the initial phase, $20,000 – $200,000 after initial phase. If the partner is public or non-profit NSERC will cover 100% of the funding cost, if the partner is private NSERC will cover 90% of the funding cost. This program is highly competitive.

Mitacs Accelerate Fellowship

Mitacs Accelerate funding supports hiring a student or post doc for a paid internship to work on a targeted, industry specific research project. The project costs are split between Mitacs and the industry partner equally, starting at $15,000 per four month term ($7,500 each).  Undergraduate students can complete two terms, graduate students can complete four, and PhD students can complete up to eight.

Mid Stage Funding

 Innovate BC Ignite Award

Innovate BC promotes market driven industry-academic research, strengthening partnerships, supporting talent development, and stimulating BC’s economic growth. Their funding award, Ignite, supplements a research project that has already secured funding from an industry partner and is well into the research phase. Ignite will share 33% of project costs up to $300,000. To be eligible a partnership must be able to demonstrate that their research solves a significant problem in industry and that it will be commercialized within 3 years.

Late Stage/Pre-Licensing  Funding

 NSERC Idea to Innovation Grant

The Idea to Innovation (I2I) grant is a late stage research grant that serves to aid the last steps before commercializing a new technology. In the early stages of the grant where there is still some research to finish, a letter of intent to transfer or license the completed technology is required from an industry partner. Here, NSERC funds 100% of project costs up to $125,000. In the later stages when the technology is being commercialized, the industry partner will lead the development of a technology transfer plan. NSERC will share 66% of project costs in this phase, up to $125,000.

When industry and academics collaborate, expertise from both sides comes together to better execute the development of a technology. Researchers can help develop and validate industry ideas, while industry can support research and commercialize technologies and vice versa. This is facilitated by the ILOs who serve as a bridge between industry and academics. They bring industry and academics together, market technologies, help explore and secure funding, and guide both parties through securing IP.  Industry-academic partnerships strengthen the development of novel ideas, and bring  expertise from a variety of areas to facilitate the commercialization process. For more information on industry-academic partnerships and connecting with an ILO please visit the UVic RPKM website.

 

 

Written by Morgan Cummingham (RPKM Co-op Student) and Liz Bueckert. 

Bringing Innovative Ideas to Life – Dr. Rishi Gupta on Reducing Porosity and Increasing Service Life of Concrete

As a teenager, UVic Professor, Rishi Gupta spent his weekends at construction sites with his father, who had a PhD in concrete technology. These weekends allowed Dr. Gupta to learn the intricacies behind creating concrete from cement, learn the impact production has on the environment, and how great ideas can become tangible, if you just put pen to paper. Dr. Gupta’s passion for the science of concrete was ignited at an early age, this passion continues to grow, and his innovations are making great strides towards stronger, cleaner infrastructure. Learn more about Dr. Gupta and his “Surface Treatment for Concrete Reinforcement” for which he has been granted a National US patent (IP No. 9908813), and is available for licensing. 

  1. Your research space is the Facility for Innovative Materials and Infrastructure Management (FIMIM), given your area of research were you always looking for an opportunity to improve the cement to concrete processes or was this a happy accident?

The idea of improving the interface of enforcement is a long standing issue. Concrete is the most used material world-wide and has been for a very long time. A perfect marriage took between concrete and steel to produce reinforced concrete that is now a very popular construction technique. Concrete is brittle and steel ductile, but steel will cause corrosion. A big portion of money these days is spent on rehabilitation of infrastructure constructed using reinforced concrete.

It was always on my mind that the use of steel as a reinforcement of concrete continues to be an issue. There is epoxy coated rebar but these are synthetic coatings and concrete has a cementitious binder, thus creating issues. I wanted to improve the bonding of reinforcement by improving the interface between the rebar and concrete. I thought, let’s replace the coating. Rather than improving the entire matrix why not put the stuff where it needs to be in the [exact area of] reinforcement, on the surface.

  1. What is the current problem with the production and life cycle of cement?

Concrete on its own can last forever. It is like an artificial stone. The problem comes when you add steel, or synthetics or glass, concrete treats all of these materials as foreign and the interface becomes weak. This interface is called the interfacial transition zones (ITZ). That’s what this innovation is focused on. The ITZ is not visible to the naked eye. This is the analogy I like to use for what is happening at the ITZ:

If you have a bunch of soccer balls in a net you can pack them up pretty closely. If you take those soccer balls and push them up against a wall they don’t pack as tightly, there are big gaps between the balls and the wall. The wall is considered the reinforcement, such as rebar, and the balls are the small cement particles. The less closely the balls pack to the wall the more pores there are. This creates many large pores right at the interface and bonding is greatly reduced. The second problem with increased porosity is that harmful elements like salt, sulfates and carbon dioxide get closer to the reinforcement faster causing weakness and increased deterioration. The environmental effect can further deteriorate the already weak ITZ. The service life of the entire structure ends up being much shorter than anticipated due to these factors.

  1. How does your patented, concrete surface treatment solve this problem?

There are well known substances that we call supplementary cementitious material (SCM). An example of SCM is fly-ash. Fly-ash is produced when coal is burned in thermal power plants. When you add this waste material to concrete it makes concrete stronger. So, it was a no-brainer to add a SCM to concrete, environmental waste is removed from the environment, a home is found for the waste, and in turn, the amount of cement used is reduced. This makes a positive global impact because the production of cement emits a lot of carbon dioxide [about 8% of the total global carbon dioxide]. There are many other SCMs some of which are very expensive. There is also silicafume which is an exceptional material that has the ability to remove lime. Limestone is put into the mixture to make concrete, but the limestone turns to lime and actually makes concrete less durable. When you add silicafume to the concrete it reacts with the lime and reduce the amount of lime in the concrete. What is great is the reaction between lime and silica produce a really amazing product that reduces deterioration.

Let’s come back to the analogy of soccer balls – if I want to improve the packing of the soccer balls I would add a SCM to concrete. If the need is to improve the ITZ, why not just add SCM into the ITZ. In other words, put it on the specific parts of the wall rather than the all over the room (or throughout the net with the balls). This would allow the reinforcement to be the carrier of SCM and when the lime is produced in the ITZ, the SCM reacts with the lime and yields calcium silicate hydrate gels, these are good gels. SCM + free lime = good gel to improve mechanical strength and makes the IT zone less porous, improving overall strength and service life.

  1. With a weakened ITZ – how long is the expected service life?

In Civil Engineering if we talk about bridges reinforced with concrete, they typically have a design life of 75 years, but what we have actually found is that bridges in North America were only lasting 40 years. This brings up the question of what is going wrong. The infrastructure owner paid for a service life of 75 years, so what happened to those additional 35 years? On closer inspection, premature deterioration is found, and a wide spread problem of corrosion. In cooler climates ice and salt cause rust and additional corrosion. This is where the service life has been lost. Just concrete it self would have a service life of 100+ years because stone lasts forever, but the tensile strength of concrete is only 10% that of steel. The tensile forces of steel and the compression forces of concrete equal the best combination for construction.

  1. How does the addition of a SCM improve the service of concrete?

 We know there will be improvement in long term durability because there are changes in the microstructure of the ITZ by eliminating lime, reducing porosity, reducing corrosion and improving durability. The whole industry has done a ton of research on concrete corrosion. We know this will greatly reduce corrosion rates.

My innovation will increases the service life of concrete, but also reduces the total amount of materials required for repairs or replacement structures. My new reinforcement is a higher end version that performs better in bond strength and lasts longer when compared to what is currently available. The amount of reinforcement is actually reduced. At this moment, it is better to assume that the amount of reinforcement remains the same but this technology adds additional benefits.

  1. How do you think this will positively impact a greener use of concrete?

Simply extending the service life of concrete structures will have a positive impact on the environment. If the addition of the SCM reinforcement allows the structure to last for the full design life (75  years) we are not replacing infrastructure as often, reducing carbon dioxide emissions and reducing the use of replacement materials. The front-end aspect is that most of the SCM are industrial waste materials such as silica fumes and fly ash. Really, any material with pozzolanic capacity could be used as the coating. If you can identify a SCM it can typically be used as a reinforcement coating material, and this allows for a cleaner, greener way to reinforce concrete and increase the service life.

  1. How do you stay inspired and spark creativity to continually generate new ideas?

My introduction to engineering happened when I was a teenager, and my father happened to have a PhD in concrete technology. I would spend my weekends hanging out on construction sites. My father would always say, “civil engineering is amazing because you have something sketched up on paper and then you get to see it come to life.” This had a life changing effect on me, and it continues to keep me inspired today. I am always thinking of new ideas. It also helps that I am also surrounded by exceptional students that help keep the creative spark alive in me.

  1. How do you clear your head after a long week in the lab?

I have a 5 year old at home and 75+ year old at home. I feel blessed to come home and unwind with my family. The kind of work that I am in is non-stop, my mind is continually going, but when I come back home to be with my family I get to detox from all that is happening in my professional life. I also really enjoy being in the moment with my 5 year old by bike riding and swimming.

To read more on this technology head over to the Research Partnerships Technology Portfolio here

 

 

Written by Liz Bueckert.

UVic Lab Quickly Pivots in a Pandemic and Joins Forces with Industry to Develop PPE

After the impact of the COVID-19 pandemic began to be fully realized, and shortages in PPE for medical professionals around the world became painfully apparent, new initiatives for locally sourced and produced supplements to the industry began to pop up. Here in Victoria, BC, the main hub for this began in the Willerth Laboratory at UVic. To get the initiative off the ground Coast Capital Savings donated a generous amount of $10,000. In addition, there was support from UVic Co-op and Career Services, Coast Capital Savings Innovation Centre, Technation, Innovate BC, UVic BME and New Venture BC to hire summer co-op students to work on the development of PPE. The community quickly pivoted to make this initiative come to life, and the UVic Engineering COVID-19 Response Team was founded. Co-ordination quickly began to start production of 3D printed face shields for the community. As well as collecting donated parts from local individuals with personal 3D printers, they have a lab full of their own 3D printers as the primary production line. All of the face shields being produced are donated to Island Health at no cost, as well as to a variety of family doctors throughout Vancouver Island.

The face shields are made up of four main parts: headband, shield, shield reinforcement, and elastic.

The headbands are the most complicated part to produce. They are 3D printed, both at UVic and by various generous members of the community. The 3D printer lab at the UVic Engineering Lab Wing currently has 9 Ultimaker printers running around the clock, to churn the headbands out as quickly as possible.

After the headbands are printed, they need to go through a rigorous testing and refining process. A rotating collection of 1-3 socially distancing co-op students separate each headband from the printed stack, smooth and sand off any rough edges or blemishes, and apply a load to make sure they are structurally sound. Health care professionals are going to be wearing the bands for hours at a time, so it is important to ensure they’re as comfortable as possible.

The elastic is much simpler to produce. While the design is constantly changing and being upgraded, the main idea stays the same. It has three tab endings that attach to the headband, and an adjustable backing connector. This allows the wearer to easily adjust the shield to fit snugly to their face as comfortably as possible. The main issue with this critical part is sourcing it: demand is high around the world, and that makes it hard to get reliably.

The shield is manufactured by a generous local business in Sidney, BC: Foreman CNC. They use a laser cutter to efficiently produce clear plastic shields with smooth edges and precise locating features for attachment to the headband. Again, the main hardship here is sourcing material. In a time when every establishment that is open has put up clear plastic barriers to protect their employees, it’s not hard to imagine that the supply of those materials is suddenly overwhelmed.  The headband has had to be redesign once already to account for using a thicker shield than originally planned after the thinner one became impossible to acquire for a number of weeks.

After manufacturing, all of the parts are sent to the second lab for sterilization and packaging. Currently, the face shields are being assembled and sterilized in the Medical Sciences Building, within the Willerth Laboratory. The newly 3D printed headbands are sanitized via soap and water; then, laid out to dry. The visors, which are not manufactured on campus, are sterilized by wiping both faces with ethanol. After both pieces have been properly sterilized, they are packaged into a transparent plastic bag along with the elastic band. In addition, to disinfect the kit further, the kits are each placed into an Ultraviolet sterilization cabinet for 15 minutes.

Furthermore, the Victoria Hand Project and two co-op students are currently testing the tensile strength of 3D printed specimens after being exposed to varying sanitization methods. Methods include ethanol, isopropyl alcohol, hydrogen peroxide, and soap; all methods that are currently being used to disinfect face shields. This study’s results will display the ideal disinfectant for reusable face shields.

The process is ever changing, and the team is constantly making adjustments to accommodate new materials and improvements to fine-tune the design are occurring regularly. The objective evolves as the they continue to optimize the design of the three-part face shield.  The question always being considered is: how can the design be improved to make the shields more easily produced, comfortable, and effective? Currently, new inserts are being produced that create a seal at the top of the visor, which further improves protection from airborne particles.

The team is managing to produce approximately 250 face shields per week at peak production, plus receiving approximately 100 donated community prints per week. To date, the team has been able to donate 2600 face shield kits to local medical professionals. With continued support from local donors and the community, they will be able to continue with this initiative as well as being prepared to provide for any new future demands in locally sourced PPE that may arise.

 

Written by Tal Katz (Willerth Lab Co-op Student) and Liz Bueckert.