Microfluidics

Using organ-on-a-chip platform, researchers devise potential strategy to treat severe COVID-19 complications

Christopher.Sorensen — Mon, 28 Mar 2022 14:43:37 +0000

Using organ-on-a-chip platform, researchers devise potential strategy to treat severe COVID-19 complications

Christopher.Sorensen Mon, 03/28/2022 - 10:43

Cutline

Professor Milica Radisic and PhD candidate Rick Lu belong to a research team that's exploring the potential of a novel anti-inflammatory peptide to prevent a potentially life-threatening immune reaction known as a cytokine storm (photo by Jennifer Kieda)

Safa Jinje

Topic

Our Community

COVID-19

Institute of Biomedical Engineering

Institutional Strategic Initiatives

Faculty of Applied Science & Engineering

Microfluidics

Research & Innovation

Using their novel organ-on-a-chip platform, a research team from the University of Toronto’s Faculty of Applied Science & Engineering has identified a molecule with the potential to combat one of the most severe complications of COVID-19 infections.

The molecule, a novel anti-inflammatory peptide called QHREDGS, does not act on the virus directly. Instead, it works to prevent a potentially life-threatening immune reaction known as a cytokine storm.

Cytokine storms are known to occur in some patients with COVID-19, as well as other illnesses. They happen when the body releases a large number of signalling proteins called cytokines in the blood. Too many cytokines push the immune system into overdrive and can lead to vascular complications, multi-organ failure and even death. One of the greatest challenges for clinicians during the COVID-19 pandemic has been understanding why some people infected by the SARS-CoV-2 virus experience cytokine storms, while others do not.

Researchers in U of T Engineering’s Centre for Research and Applications in Fluidic Technologies (CRAFT), co-led by Professor Milica Radisic of the Institute of Biomedical Engineering and the department of chemical engineering and applied chemistry, are leveraging their expertise in organ-on-a-chip technology to study the problem.

“Human cell-based organ-on-a-chip systems have a unique advantage of enabling us to dissect complex processes by simplifying the system and strategically introducing various immune cell types to understand the cascade of events better,” says Radisic.

Radisic and her team are experts in growing functional cardiac tissue outside the human body. These lab-grown tissues allow researchers to model diseases and understand how genetic mutations in cardiac tissues can cause cardiac failures.

“During the pandemic, we repurposed our cardiac tissue platforms to understand how the SARS-CoV-2 virus can cause vascular dysfunction,” says Rick Lu, a PhD candidate.

In a recent paper published in the journal Lab on a Chip, Lu and his co-authors demonstrated how they carried out the study using a specific model tissue platform known as integrated vasculature for assessing dynamic events (InVADE) – an investigation that was supported by U of T’s Connaught Fund, the Toronto Innovation Acceleration Partners and a donor to the university.

Using the InVADE platform, they infected a microfabricated perfusable blood vessel-on-a-chip with SARS-CoV-2 to understand how the virus triggers inflammation and vascular dysfunction.

They also screened five compounds with anti-inflammatory properties that had been previously tested by clinicians to see if any of them showed promise in preventing the cytokine storm.

QHREDGS is a peptide that had previously been found to improve cardiomyocyte metabolism and enhance endothelial cell survival. In the study, Lu found that it enhanced vascular functions and repaired the harmful effects of SARS-CoV-2. For example, the function of a vascular structure known as the endothelial barrier was improved by 62 per cent compared with endothelial cells without the peptide, and the secretion of some cytokine storm molecules had been decreased between1,000 to 10,000 times.

“Vascular dysfunction can allow SARS-CoV-2 to penetrate into a person’s organs, such as the heart, liver and intestine,” says Lu. “By improving vascular function and reducing inflammation in the body, we hope to prevent the kind of organ failure that has been seen in COVID-19 patients.”

The InVADE platform is being used for many other investigations in Radisic’s lab, including a study that explores why cancer is rarely found in the heart. Lu and his colleagues are also using the vasculature-on-a-chip system to better understand the causes of myocarditis that have been seen in COVID-19 patients, as well as in some individuals who have been vaccinated against the disease.

The team is currently collaborating with clinicians and researchers across Toronto to find unique biomolecular markers associated with myocarditis.

“We’re currently using some of the innate immune system – namely the peripheral blood mononuclear cells (PBMC) and neutrophils – to see how those immune cells can cross-talk with cardiac tissue to understand how they affect the cardiac tissue function,” says Lu.

“We’re really excited about this because not only will we be able to identify some of the molecular pathways associated with myocarditis, but we also hope to find potential therapeutics to reverse this inflammation in the heart.”

Radisic hopes this type of organ-on-a-chip system will enable researchers to predict and better respond to future public health events.

“Besides eliminating animal studies and keeping the participants in clinical studies safe, [the system’s] small scale also enables us to be efficient in reagent use, as well as safe by minimizing the amount of virus that is needed to carry out the experiments,” she says.

“This technology can enable quick and efficient studies of emerging pathogens and their potential to infect and impair function of various human organs.”

CRAFT Device Foundry at U of T ushers in new era of microfluidic device fabrication

Christopher.Sorensen — Tue, 14 Dec 2021 18:06:21 +0000

CRAFT Device Foundry at U of T ushers in new era of microfluidic device fabrication

Christopher.Sorensen Tue, 12/14/2021 - 13:06

Cutline

The new CRAFT Device Foundry at U of T will bring together researchers, clinicians, entrepreneurs and industry collaborators and support large-scale fabrication of biomedical devices (photo by Daria Perevezentsev)

Lynsey Mellon

Topic

Our Community

Chemistry

Faculty of Applied Science & Engineering

Faculty of Arts & Science

Microfluidics

Research & Innovation

The Centre for Research and Applications in Fluidic Technologies (CRAFT) – a partnership between the University of Toronto and the National Research Council of Canada (NRC) – has launched a new research facility on U of T’s St. George campus.

The Device Foundry will bring together researchers, clinicians, entrepreneurs and industry collaborators with a goal of advancing micro-nano fluidic device fabrication. Housing equipment to support large-scale production of biomedical devices, the facility has the capability to quickly commercialize new technologies in health care.

“The opening of the new Device Foundry marks a huge milestone for CRAFT,” said Axel Guenther, a professor of mechanical engineering in the Faculty of Applied Science & Engineering and the co-director of CRAFT.

“Many individuals from U of T and the NRC came together to make this unique space a reality. With the launch of this open-research facility, we are now well positioned to advance the field of microfluidics and serve as a hub for collaborations that will bring innovative technologies to the health-care community.”

Iain Stewart, president of NRC, toured the new facility this week with senior U of T leaders and researchers, stopping to visit the Device Foundry’s lithography cleanroom, fabrication room and the 3D printing station.

Iain Stewart, president of the National Research Council of Canada, met with senior U of T leaders and researchers (photo by Dahlia Katz)

In her welcoming remarks, Christine Allen, associate vice-president and vice-provost, strategic initiatives, said the national hub will leverage U of T’s multidisciplinary strengths and provide “unparalleled hands-on learning opportunities,” to students and post-doctoral researchers.

Allen added that the investment “will translate into clinical device innovations and position Canada at the forefront of the microfluidics field.”

The Device Foundry is set up to rapidly produce and deploy polymer-based biomedical microdevices, including organ-on-a-chip models of heart tissues and handheld 3D skin printers. The facility features a new micro-injection molder that will allow for thousands of micro-fluidic devices to be created every hour, a micro-milling machine for creating molds, a roll-to-roll polymer coater, multiple embossers, a laser cutter, a glass 3D printer and a nano-scale 3D printer.

“Congratulations to the CRAFT team for the opening of the new facility in Toronto,” said Teodor Veres, co-director of CRAFT and R&D director of the Medical Devices Research Centre at the NRC. “This space adds significant technological and scientific assets to the existing world-class microfluidic device R&D capacity at NRC in Boucherville, Que.

“Together, these two CRAFT labs will enable the development, deployment and validation in clinics of emerging lab-on-chip systems made in Canada.”

Christine Allen, associate vice-president and vice-provost, strategic initiatives, said the new facility will provide “unparalleled hands-on learning opportunities” (photo by Dahlia Katz)

U of T has one of the world’s largest microfluidic device research communities with more that 50 investigators, including CRAFT co-leads Milica Radisic, a professor in the department of chemical engineering and applied chemistry and the Institute of Biomedical Engineering, and Aaron Wheeler, a professor in the department of chemistry in the Faculty of Arts & Science and the Institute of Biomedical Engineering who is also affiliated with the Donnelly Centre for Cellular and Biomolecular Research, where his lab is located.

The NRC in Boucherville, meanwhile, has 40 scientists contributing to micro-nano device research in areas such as diagnostics, precision medicine and cell-based therapy.

“The hope is for the spirit of collaboration that went into creating CRAFT, and this new space, to be reflected in the work that comes out of it,” said Guenther. “With the investment from the NRC, we now have dedicated technician support to train students, maintain the equipment and help researchers and start-ups bring their devices directly to the communities that will use them.”

Added Veres: “CRAFT will aid Canada’s medical device sector growth and support the discovery of new knowledge that can be translated into innovative technology-driven products, processes and services. The Device Foundry will also offer a unique work-integrated learning environment and development opportunities for the workforce of the future, keeping our highly-trained personnel in Canada.”

U of T in focus: The year in pictures

geoff.vendeville — Wed, 19 Dec 2018 05:00:00 +0000

U of T in focus: The year in pictures

geoff.vendeville Wed, 12/19/2018 - 00:00

Cutline

Mason Godkewitsch, 8, makes shadow puppets on the walls of the “cell cave” in the student lounge in the McLennan building on the downtown Toronto campus (photo by Geoffrey Vendeville)

Topic

Canada Research Chairs

Faculty & Staff

Faculty of Applied Science & Engineering

Research & Innovation

STEM

U of T Mississauga

U of T Scarborough

Undergraduate Students

University College

In the lab, classrooms and at a variety of events on the three University of Toronto campuses, U of T News photographers captured moments that made this year special.

Staff photographer Nick Iwanyshyn selected some of the highlights of 2018.

Axel Guenther, scientific director of the Centre for Microfluidic Systems, inspects microfluidic devices in a cleanroom. This fall, U of T partnered with Canada’s National Research Council to create a national innovation hub focused on microfluidics (photo by Nick Iwanyshyn)

Students line up before making a grand entrance at the second student-led Black graduation ceremony in June at Hart House. In 2017, U of T became the first Canadian university to host a Black graduation (photo by Geoffrey Vendeville)

Foreign Affairs Minister Chrystia Freeland looks on during a service of remembrance at the University of Toronto's downtown campus (photo by Nick Iwanyshyn)

Alán Aspuru-Guzik, who came to U of T from Harvard University to become a Canada 150 Research Chair, delivered the keynote address at the University of Toronto-Tsinghua University Entrepreneurship and Innovation Forum in May (photo by Chris Sorensen)

Elspeth Arbow, an undergraduate student with cystic fibrosis recovering from her second double-lung transplant, gets ready for physiotherapy at Toronto General Hospital on May 4 (photo by Geoffrey Vendeville)

Wearing matching maple leaf socks, former U.S. vice-president Al Gore and former Google CEO Eric Schmidt chat on the main stage at the Elevate technology conference in Toronto, on Sept. 26 (photo by Chris Sorensen)

Your mind isn't playing tricks on you. Students go up the stairs at U of T Scarborough (photo by Nick Iwanyshyn)

Kirsty Duncan, minister of science and sport, watches a demonstration during a Nov. 13 announcement about new and renewed chairs in the Canada Research Chairs program, including 21 at U of T (photo by Nick Iwanyshyn)

Cranes in the colours of the rainbow hang from a window at Hart House's reading room in June to mark Pride (photo by Romi Levine)

Students gather to study and chat at U of T Mississauga (photo by Nick Iwanyshyn)

Enakshi Shah, who earned a bachelor's degree in chemical engineering at U of T, found there were lots of opportunities after graduating (photo by Nick Iwanyshyn)

A girl adds to a poster about what it means to be a woman in science, technology, engineering and math (STEM) at Science Rendezvous on May 12 (photo by Geoffrey Vendeville).

Hundreds of people in a rainbow of colours filled the Goldring Centre for High Performance Sport at the University of Toronto for the Indigenous Studies Students' Union's powwow on March 11 (photo by Laura Pedersen)

For Remembrance Day and the 100^th anniversary of the armistice ending the First World War, U of T News staff photographer Nick Iwanyshyn juxtaposed archival campus photos with present-day pictures at the same location. Above, a Sopwith Camel plane appears in front of University College in 1918 (photo illustration includes a U of T Archives photograph)

Members of the U of T community gather outside of University College on Oct. 30 for a vigil for victims of the attack on the Tree of Life synagogue in Pittsburgh (photo by Romi Levine)

Astrophysicist Matt Russo makes music using the movements of objects in space. The music was featured in Our Musical Universe, an audio-focused planetarium show that debuted at U of T in January (photo by Romi Levine)

Drummers welcome delegates during a Spiritual Opening Ceremony for the Parliament of the World’s Religions around the Sacred Fire in Olympic Park, on Nov. 2 (photo by Nick Iwanyshyn)

Rose Patten, centre, U of T's 34th chancellor, was installed in a ceremony in November (photo by Nick Iwanyshyn)

At the 25th annual Bring Our Children to Work Day on April 26, kids got to see a soda geyser made of Mentos and cola spraying 12 feet above the courtyard near Lash Miller Chemical Laboratories (photo by Geoffrey Vendeville)

U of T partners with National Research Council to create national innovation hub for microfluidics

noreen.rasbach — Mon, 26 Nov 2018 14:31:30 +0000

U of T partners with National Research Council to create national innovation hub for microfluidics

noreen.rasbach Mon, 11/26/2018 - 09:31

Cutline

Axel Guenther’s team used microfluidic technology to create a handheld 3D skin printer that deposits layers of skin tissue to cover and heal deep wounds (photo by Nick Iwanyshyn)

Topic

Faculty of Applied Science & Engineering

Faculty of Arts & Science

Microfluidics

Research & Innovation

The University of Toronto is partnering with Canada’s National Research Council to create a national innovation hub focused on microfluidics – a field in which tiny amounts of fluid are manipulated in small-scale devices to create everything from portable diagnostic “labs” to repair kits for human organs.

The new hub, called the Centre for Research and Applications in Fluidic Technologies, or CRAFT, will combine the talents of U of T microfluidic experts and NRC scientists in a bid to catalyze new discoveries and scale up production of existing prototypes to deliver higher quality patient care at a lower cost.

In total, CRAFT will involve more than 200 people, 45 labs and 25 technology companies, and will be jointly funded by both partners with a $22 million investment over five years.

“This partnership between the NRC and the University of Toronto will deliver a tangible impact on the lives of Canadians by developing and commercializing biomedical technologies that improve care for patients while reducing costs for the Canadian health system,” said Vivek Goel, U of T’s vice-president of research and innovation.

“The interactions between our lead researchers and NRC scientists in the field will also offer valuable applied research experience and training opportunities for our students and young investigators.”

Both U of T researchers and NRC scientists are world leaders in microfluidics, which involves mixing tiny amounts of fluid on a small chip to achieve desired chemical or physical reactions, or to grow live cells in an environment that mimics the inside of the human body. By joining forces, the new CRAFT platform – the first NRC collaboration of its kind – is expected to generate new publicly held patents and scientific publications. It also aims to bolster Canada’s medical devices and manufacturing industries, making them more competitive internationally.

In particular, CRAFT will focus on using microfluidic technologies to make advances in the following key areas: shrinking the functions of medical laboratories onto a single small chip, allowing for rapid diagnosis of diseases; growing organ tissues on devices outside the body to test drugs or do research related to personalized medicine; and printing biological tissues that can be used to repair organs of the human body.

“Toronto is one of the leading centres in the world for this kind of research,” says Axel Guenther, an associate professor in U of T’s Faculty of Applied Science & Engineering who is the scientific director of Toronto’s Centre for Microfluidic Systems, and one of the lead researchers involved with the CRAFT collaboration.

“There are more than 30 teams working on these kinds of devices, including at U of T and in our partner hospitals.”

Axel Guenther, scientific director in the Centre for Microfluidic Systems, inspects microfluidic devices in a cleanroom (photo by Nick Iwanyshyn)

Guenther’s team, for example, used microfluidic technology to create a handheld 3D skin printer that deposits layers of skin tissue to cover and heal deep wounds. The size of a small shoebox, the device weighs less than a kilogram and functions like a white-out tape dispenser that deposits thin sheets of skin tissue.

Milica Radisic, a professor in the department of chemical engineering who is the Canada Research Chair in Functional Cardiovascular Tissue Engineering, and Aaron Wheeler, a professor in the department of chemistry who is the Canada Research Chair of Bioanalytical Chemistry, will also play key roles in the CRAFT collaboration. Radisic has developed an injectable patch, which can be seeded with heart cells from a patient’s own body, to repair tissues damaged during a heart attack without resorting to open-heart surgery. Wheeler’s team, meanwhile, has developed a portable “lab-on-a-chip” diagnostic platform that brings the power of a diagnostic laboratory into the field, where it was used to gauge the level of immunity to vaccine-preventable diseases in remote regions of Kenya.

Yet all of these technologies currently exist as prototypes only. Getting them ready for clinical application will require significantly ramping up production.

Vivek Goel, U of T’s vice-president of research and innovation, with Roman Szumski, vice-president of life sciences at the National Research Council (photo by Tristan McGuirk)

“When a student develops something, it’s usually made by hand – it’s an artisanal device,” explains Radisic. “If you want it to be something that’s used across an entire industry, you need to be able to make thousands at a time. And it’s time-sensitive: If you don’t do it quickly enough, the window of opportunity closes.”

Hence, the vision for CRAFT is to create a leading-edge facility capable of bringing microfluidic technologies from lab-scale prototypes to commercially viable products.

To get there, microfabrication equipment from the three U of T labs will be consolidated and expanded with new machines capable of manufacturing thousands of units. Graduate students and researchers from U of T and its partner hospitals will work alongside NRC scientists and technologists with experience in the development of medical devices. They will also draw extensively on the expertise and manufacturing capabilities of NRC’s existing Medical Devices Research Centre in Boucherville, Que.

“When our students can interact one-on-one with experts in scale-up and commercialization, it gives us a huge advantage,” says Wheeler. “It means we can overcome any obstacles to application right away, which in turn enables us to get new technologies into the clinic much faster.”

NRC has deep expertise working with the unique materials needed to construct microfluidic devices at scale.

Milica Radisic, the Canada Research Chair in Functional Cardiovascular Tissue Engineering, will play a key role in the CRAFT collaboration. She attended Monday's announcement (photo by Tristan McGuirk)

“Many researchers build their prototypes out of a material called polydimethylsiloxane (PDMS),” says Radisic. “It’s easy to work with in the lab, but it absorbs small molecules, including drugs, which means we can’t use it for the commercial versions. NRC scientists know how to make devices from other thermoplastic elastomers that don’t absorb small molecules.

“That would be a game changer for us.”

Guenther expects that over the next five years, CRAFT will spawn a number of spinoff companies. He also emphasizes that collaboration – between researchers, technologists and clinicians – will be key to CRAFT’s success.

“This will be an open facility, accessible to everyone who is working in this technology space,” says Guenther.

“Commercialization is something that cannot be done by engineers alone. A good project is one where clinicians have strong opinions about the engineering, and engineers have an in-depth understanding of clinical reality. I have seen this quite frequently – it really makes all the difference.”