Lab-on-a-chip detects ovarian cancer with a liquid biopsy

Researchers at the University of Kansas (KU) have developed an ultrasensitive diagnostic device, or lab-on-a-chip, that could allow doctors to detect cancer quickly from a droplet of blood or plasma — leading to timelier interventions and better outcomes for patients.

Described in the journal Nature Biomedical Engineering, the lab-on-a-chip is designed to detect exosomes — tiny parcels of biological information produced by tumour cells to stimulate tumour growth or metastasize. As explained by lead author Yong Zeng, exosomes were originally believed to be “trash bags that cells could use to dump unwanted cellular contents — but in the past decade, scientists realised they were quite useful for sending messages to recipient cells and communicating molecular information important in many biological functions”.

“Basically, tumours send out exosomes packaging active molecules that mirror the biological features of the parental cells,” Zeng said. “While all cells produce exosomes, tumour cells are really active compared to normal cells.”

The lab-on-a-chip utilised a 3D nanoengineering method that mixes and senses biological elements based on a herringbone pattern commonly found in nature, efficiently pushing exosomes into contact with the chip’s sensing surface in a process called ‘mass transfer’.

“People have developed smart ideas to improve mass transfer in microscale channels, but when particles are moving closer to the sensor surface, they’re separated by a small gap of liquid that creates increasing hydrodynamic resistance,” Zeng said. “Here, we developed a 3D nanoporous herringbone structure that can drain the liquid in that gap to bring the particles in hard contact with the surface where probes can recognise and capture them.”

Zeng compared the chip’s nanopores to a million little kitchen sinks: “If you have a sink filled with water and many balls floating on the surface, how do you get all the balls in contact with the bottom of the sink where sensors could analyse them? The easiest way is to drain the water.”

To develop and test the microfluidic device, Zeng teamed with KU Cancer Center Deputy Director Andrew Godwin, as well as graduate student Ashley Tetlow, in Godwin’s Biomarker Discovery Lab. The collaborators tested the chip’s design using clinical samples from ovarian cancer patients, finding the chip could detect the presence of cancer in a minuscule amount of plasma.

“Our collaborative studies continue to bear fruit and advance an area crucial in cancer research and patient care — namely, innovative tools for early detection,” Godwin said. “This area of study is especially important for cancers such as ovarian, given the vast majority of women are diagnosed at an advanced stage when, sadly, the disease is for the most part incurable.”

What’s more, the KU microfluidic chips would be cheaper and easier to make than comparable designs, allowing for wider and less-costly testing for patients.

“What we created here is a 3D nanopatterning method without the need for any fancy nanofabrication equipment — an undergraduate or even a high school student can do it in my lab,” Zeng said. “This is so simple and low-cost it has great potential to translate into clinical settings.”

With the microfluidic chip’s design now proven using ovarian cancer as a model, Zeng believes the chip could be useful in detecting a host of other diseases. He said he has been collaborating with Godwin and other research labs and departments at KU in order to further explore the translational applications of the technology.

“Now we’re looking at cell-culture models, animal models and also clinical patient samples, so we are truly doing some translational research to move the device from the lab setting to more clinical applications,” he said. “Almost all mammalian cells release exosomes, so the application is not just limited to ovarian cancer or any one type of cancer. We’re working with people to look at neurodegenerative diseases, breast and colorectal cancers, for example.”

Image credit: Yong Zeng.

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