Sydney Laput
Yanyu Xiong, a graduate student studying electrical and computer engineering, holds the photonic crystal biosensors which is what holds the droplets of liquid to perform the tests.
September 21, 2022
When Brian Cunningham, professor in Engineering, was in his thirties, his parents passed away from cancer. He saw doctors struggle to diagnose cancer types and assess whether treatments worked. He then decided to dedicate his engineering career to cancer research.
Now, years later, Cunningham and his colleagues invented a new way to help clinicians diagnose cancer at early stages and choose the most effective treatments for patients.
According to Cunningham, this new method features a liquid biopsy that detects individual microRNA in blood. He explained that microRNA are molecules originating from cancer cells and revealing cancer mutations.
“Ordinarily, a biopsy is used to remove tissue, like a tumor, and then to look at the cells by a pathologist,” Cunningham said. “But in a liquid biopsy, we’re seeking to take a small volume of blood out of your arm or finger and then test for the presence of molecules, whose concentration can tell the severity of cancer.”
Yanyu Xiong, a graduate student studying electrical and computer engineering and leading author of the research, said her mother was once diagnosed with cancer and later recovered. She said patients have to go through painful chemotherapy and numerous other tests to see the effectiveness of their treatments. Xiong said it usually takes such a long time that some patients may not be able to live through it.
“The earliest you can detect it, the better chance for people to stay alive,” she said. “That’s the first thing that we want to develop — something that can detect cancer at an early stage.”
However, Cunningham said it is challenging to identify microRNA in the blood of early-stage cancer patients — the small number of cancer cells in their bodies leads to a low concentration of microRNA that is hard to monitor. To solve this problem, Andrew Smith, professor in Engineering, applied quantum dots to count individual molecules.
Smith defined a quantum dot as a tiny piece of a crystal. He explained it as a bluish emerald shrunk into a 10-nanometer crystal semiconductor, a unique material that allows scientists to change all its attributes, including colors and electrical conductivity.
Smith said that in this study, quantum dots were tuned to emit light. The research team attaches these luminous quantum dots to microRNA, captures them on a biosensor and measures these molecules by counting the bright spots in the image.
“That digital counting is what makes them very, very useful for this application,” Smith said. “You can be very sure of exactly the number that’s present. That doesn’t really happen for other types of light-emitting materials. It’s the fact that quantum lights are very bright — we’ve engineered them to be emitting this very specific color range that we can measure.”
Smith noted that combining quantum dots and photonic crystals further improves the test outcomes. He compared a photonic crystal to a narrow-shaped lawn with plenty of ditches where tiny quantum dots fit in. He said the two materials resonate and dramatically amplify signals that make microRNA easy to detect with low-cost instruments.
Xiong emphasized the significance of photonic crystals. She likened quantum dots to blinking stars in the night sky. To obtain accurate data, Xiong said she used to spend hours capturing numerous images with fast shutter speeds. She said the application of photonic crystals successfully tackles this difficulty in this study.
“We found in the photonic crystal, (quantum dots) do not blink anymore, and they’re less than before,” Xiong said. “All those findings help us to visualize single molecules using an objective lens.”
According to Smith, this study is a milestone of multi-year cancer research initiated by Manish Kohli, a cancer clinician and researcher at Huntsman Cancer Institute in Utah. Smith said he has worked with Kohli and Cunningham since 2016 on castration-resistant prostate cancer, which leaves patients only a year to live and is considered incurable.
Smith said the team has been attempting to fill the clinical care gaps by using technology to help doctors quickly determine treatments.
“You want to be able to decide if this therapy given to this patient is responding or not,” Smith said. “But you don’t know until they recur, and that stage is almost too late. So, you want some rapid tests that within a couple of days of treatment, you could tell if it’s the right treatment for a patient.”
Kohli expected the new liquid biopsy could replace pathologic complete response, or PCR, the traditional technique to identify microRNA. He said PCR is highly laborious and time consuming as clinicians must ship plenty of blood samples to laboratories with high-end, expensive instruments.
With this new technique, Kohli said clinics can assess a cancer patient’s condition with one or two drops of blood from a pinprick on their finger. He envisioned a device that can upload the microRNA counts onto the cloud and send the information to doctors hundreds of miles away.
Smith added that the research team aims to make the liquid biopsy a simple, regular test that can be done frequently during cancer treatments.
“That’s something revolutionary in many ways,” Kohli said.
According to Cunningham, the team will be conducting trials on blood samples collected from 100 patients at Kohli’s clinic with various stages of prostate cancer. Cunningham said they will verify this new technique’s superiority by comparing it with other existing methods of identifying molecules.
Kohli recalled that it took time for the research team to understand each other when they first met. He said each member’s expertise in medicine and bioengineering was once isolated, but he knew the more their specialties get united, the better research products they will offer patients.
“Otherwise, the application of these sciences will fall short of their potential,” Kolhi said. “There are 1000 questions to ask cancer researchers, and we don’t have great technology being applied. We’ve successfully done many projects together, and we are going to build on that as we keep moving forward.”
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