Updated: Sep 9, 2020
In 2020, roughly 1.8 million people will be diagnosed with cancer in the United States. In an ideal world, each and every one of them would be able to receive individualized treatment that targets the right kind of cells in the right kind of ways to save lives and make them healthier.
That’s one of the ideas behind Microcosm, an Invent Oregon finalist that has designed a new kind of testing platform that will allow medical labs to test cellular behavior more quickly and more accurately.
"Imagine the current way of testing,” said Avathamsa Athirasala, a Ph.D. candidate at OHSU’s Bertassoni Lab and the principal researcher at Microcosm. "I would test one sample one way, and that would be a full experiment. But with our technology, you test one sample that contains 50 different ways of testing and you test it all in parallel.”
Traditionally, tissue research takes place in a two-dimensional environment. Samples are prepared in a rigid plastic dish, where they spread out and form a two-dimensional structure.
“That's not really what cells are like in the body,” Athirasala said. “They're in a three dimensional system. They're not in these little neat perfect balls either. They have all kinds of shapes and sizes.”
This kind of cellular variability is not accounted for in the typical lab setting. In the body, different types of tissue have different properties. Bones are stiff, for example, which reflects their level of mineralization and the function that bone performs. Fat, on the other hand, is soft. With each type of tissue, cells have different properties and act differently depending on their context.
“We've seen that if you put cells on the surface that is soft like cream cheese, they become softer cells, like fat or brain cells,” Athirasala said. “If you put them on something that's really hard, they become like hard cells. They become bone cells.” But because tests do not account for a cell’s environment, researchers can’t test potential treatment options that could save lives.
Like a telescope, Microcosm would allow medical researchers like Athirasala and Tahayeri to probe the human cosmos, its cells and organizations as diverse and myriad as the stars, with a simple and small device that can be used to scan the infinitude of the human universe in multiple places and multiple ways, all at once.
This type of experimental modeling is kind of like looking through the Hubble Space Telescope when all we’ve had before is a pair of binoculars—and we can actually control the conditions of the universe we’re peering into.
“We've learned in our field that when you're working with stem cells, if you have a different environment, they act completely differently,” said Anthony Tahayeri, research assistant and biological engineering graduate of Oregon State University. “You can take a single stem cell and you could turn it into an adipose tissue or you could turn it into neurons depending on how you culture it.”
Athirasala and Tahayeri work with a kind of non-invasive stem cell called HUVECs, human umbilical cord endothelial cells, which are responsibly sourced. “If you actually modify it and control it, you can guide your direction of how the tissue actually evolves.”
According to Tahayeri, Microcosm shows the most promise in the area of cancer research. Cancer likes to target specific kinds of cells based on how stiff or mineralized they are. Cancer itself is a stiff tissue; that’s how it is identified.
With Microcosm and a given kind of cancer, Athirasala and Tahayeri can actually test how that cancer will respond in different cellular environments. If a cancer likes soft tissue, they will be able to reproduce that environment experimentally. If a cancer likes mineralized tissue, like bones, they will be able to reproduce that as well.
“If we take an environment where we have that such cell and we vary the stiffness,” Tahayeri said, “we can actually test and see how much cancer wants to invade into those different types of cells. So we can model different types of cancer, see how they're penetrating in the body, and we can actually target treatments that say, oh, we see that this cancer likes to go through the very soft cells. We can target treatment that goes specifically for those soft cells and we can leave the harder cells alone, being less and less intrusive on the body when we actually provide treatment.”
For the patient, this means that highly individualized forms of disease can be confronted with highly individualized, less invasive forms of treatment, developed in a lab that can use Microcosm to test treatments in conditions that mimic the actual human cellular environment with actual cancer cells.
That’s revolutionary for patient outcomes and terrible for conditions like cancer.
In one promising example called organs on a chip, a medical lab can biopsy a small section of a patient’s tissue and synthesize miniature copies. With Microcosm, the lab could test these tissue samples against a lot of different drugs all at the same time.
“It helps with personalized medicine,” Athirasala explained, "because if you think that patient cells are behaving differently and you don't know how to predict that, you can use a tiny sample from a patient and test a whole bunch of conditions, way fast, way easier.”
But Microcosm may benefit patients as much as pharmaceutical companies. According to the National Cancer Institute, the cost of most cancer drugs released between 2009 and 2014 surpasses $100,000 per patient per year. “Especially with these new research-and-development stage drugs, they're extremely expensive to make. They really don't have that much,” Tahayeri said.
Most experiments test one drug at a time, but that isn’t where the real value lies.
"They're really interested in testing two drugs, three drugs, seeing how they actually interact with each other,” Tahayeri said. With Microcosm, that is now possible. “We can now find that, hey, these three drugs in combination, we can't test in a person, we don't know what the results might be. But in the lab, they show some promise.”
These medications may not be mass-produced or cost-efficient, but Microcosm expands the amount that we can know about different treatment options while making it more cost-effective to test them.
The implications could be far reaching for the little microcosm that mimics the human body, where the invention gets its name. “It's a little microcosm of cells that interact,” Tahayeri said. “They see each other. And they react to whatever stimulus we give to them afterwards.”