Stopping COVID-19 with Mini Models Using the “Organ-on-a-Chip” Approach
A team of Canadian researchers is building miniature models of the human nose, eyes, mouth and lungs to understand how COVID-19 gets past these organs’ defenses. These models employ the “organ-on-a-chip” approach, with researchers placing human cells from a specific organ on to a polymer chip. The researchers then introduce air containing the virus to the cells. When the cells respond to the virus, the researchers observe why the cells’ attacks are ineffective.
The team is composed of researchers from universities, hospitals, and the National Research Council of Canada (NRC) at the Centre for Research and Application in Fluidic Technologies (CRAFT). Dr. Milica Radisic, who is a member of the team, previously utilized the chip approach to regenerate heart cells.
Radisic, who is a professor in the Department of Chemical Engineering and Applied Chemistry at the University of Toronto, said the chips allow researchers to understand the virus without risking harm.
“That’s the beauty of it. We can do our research early in the viral infection. You can’t do that with a human. Once you know you have COVID-19, you’ve been infected for two weeks. With organ-on-a-chip, we can study what happens within 24 hours of COVID-19 entering the body,” said Radisic.
Shown above: a) schematic representation of the “Power Blade” centrifugal microfluidics principles; b) laboratory version of the “Power Blade” hardware with PCR cycling built-in capability (tested in parabolic flight conditions); and c) Power Blade operated polymer microfluidic device (5 x 10 cm) performing bacterial lysis, with on-chip DNA amplification implementing a molecular assay for VTEC E. coli molecular subtyping.
“Organ-on-a-chip” approach to fabricate engineered heart/cardiac tissue.
The Design of an “Organ-on-a-Chip”
Each polymer “organ-on-a-chip” contains microfluidic tubes. The tubes, each less than a millimeter in diameter, are lined with human cells and arranged in complex patterns. The researchers pump in nutrients, blood and air through the tubes. The cells then mimic the functions of a living organ.
Chips allow cell growth and maintenance under controlled conditions. They also allow researchers to test the effectiveness of drugs. In addition, they provide a way for researchers to manipulate the physical environment of the cells. For example, the researchers can vary the pressure of blood flowing in the chip. They can then monitor how well the cells are responding.
The live virus will be supplied by Dr. Karen Mossman, professor of pathology and molecular medicine at McMaster University.
“Karen has the live virus, so we will give her the chips. She will infect the organs in a special level three facility,” explained Radisic.
Incorporating Power-Blade
The researchers are also studying COVID-19 with a centrifugal actuation method called “Power-Blade.” The method involves placing a programmable air pump and multiple electromechanical valves on a rotating stage. The researchers then connect the pump and valves to microfluidic devices. Microfluidic devices are devices that manipulate and control liquid amounts in the range of microliters (10-6) to picoliters (10-12).
The researchers then computer control the valves, pump and other elements of the machine while the platform is rotating at high speed. The rotation triggers fluid displacements inside the microfluidic devices. The Power-Blade method allows the researchers to see which molecules are biomarkers for severe cases of COVID-19.
“Once we figure (the biomarkers) out ... the Power-Blade will be able to read that at point of care,” said Radisic.
Before being repurposed for research on COVID-19, the Power-Blade was being utilized to test the blood of astronauts on space missions.
Factors Beyond Cells
The researchers’ objective is to understand why epithelial barriers in the nose, eyes, mouth and lungs are not stopping COVID-19. The term “epithelial” refers to the tissue on the outer layer of the body’s surface, like the lining of the nose.
There are more factors in the body’s fight against COVID-19 than just the basic functions of cells in the organs. Surrounding conditions can make a difference. For example, cooler temperatures impair the ability of cells in the lining of the nose to protect against the common cold virus.
The population of beneficial microorganisms also has an effect. Beneficial microorganisms will attack and kill a virus. If a patient does not have enough beneficial microorganisms, the patient has less of a defense against viruses.
Although there is much more to learn, understanding how certain organs fight COVID-19 will be extremely useful. Radisic said the team wants to determine “the innate early response” of the immune system to COVID-19.
“We are all born with innate immunity. This works early when we are invaded with a virus. It finds things that don’t belong in your body and tries to clean it up,” said Radisic.