New chip could improve cancer treatment

Cancer spreads via circulating tumour cells (CTCs) that travel through the blood to other organs and are nearly impossible to track. Researchers at the Georgia Institute of Technology believe their detection method could lead to earlier and more targeted treatment, beginning with a simple blood test.

When a tumour starts metastasising, it sheds its cell into the blood. An individual cell often does not survive the bloodstream on its own, but clusters of cells are much more robust and can travel to other organs, effectively pushing the cancer to a metastatic state.

CTCs have proven difficult to study, let alone treat. Blood contains billions of cells per millilitre, and only a handful of those cells would be CTCs in a patient with metastatic cancer. Such intense filtration has been inaccessible using conventional lab methods. Most traditional filtration is too aggressive and would break the cluster back into single cells, ruining the ability to study the effect of a cluster.

“That’s what got engineers like me interested in this because we are really good at creating sensors, or small devices that actually do sensitive analysis,” said Fatih Sarioglu, associate professor at Georgia’s School of Electrical and Computer Engineering.

Described in Nature Communications, the team’s novel chip is named the Cluster-Well. According to researchers, it combines the precision of microfluidic chips with the efficiency of membrane filtration to find CTC clusters. Using micron-sized features, microfluidic chips can precisely locate each cell in a blood sample and determine if it’s cancerous.

“Microfluidic chips give you more control as a designer to actually ask whatever question that you want to ask those cells,” Sarioglu said in a statement. “It increases the precision and sensitivity, which is what you need for an application like this because you want to find that single cell out of many blood cells.”

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To rapidly process a clinically relevant volume of blood, researchers relied on membrane filtration to make the chip operation more scalable. In effect, the chip looks like a standard membrane filter, but under an electron microscope the microfluidic chip reveals its delicate structure used to capture clusters while letting other blood cells pass through.

Although the chip is initially fabricated with silicon just like a central processing unit in a computer, it is later transferred to polymers to make it accessible, affordable, and single-use, while still retaining its delicacy and precision, the team said.

“We really created only the traps that we need to have for recognising the clusters with the microfluidic chip, and the rest is just a standard filter holder,” Sarioglu said. “Compared to a conventional microfluidic chip, you will get a much more practical assay with orders of magnitude improvement in throughput and a higher sensitivity.”

Researchers used the chip to screen blood samples from patients with ovarian or prostate cancers through a partnership with the Emory and Northside Hospitals. They isolated CTC clusters ranging from two to 100 or more cells from prostate and ovarian cancer patients and used RNA sequencing to analyse a subset.

The chip’s unique design means CTC clusters are filtered in microwells and can later be accessed for further analysis. Even a single CTC can contain a significant amount of data on the patient and their specific cancer, which can be critical for managing the disease. 

For example, the researchers noted hundreds of CTCs in clusters in the blood of ovarian cancer patients, some still alive, a finding that could be consequential to the spread of the disease. Also, by sequencing the RNA in prostate CTC clusters isolated by the chip, the researchers identified specific genes expressed by these metastasising cells. 

CTC clusters from different patients were shown to express different genes, which can be potentially utilised to develop personalised, targeted therapies. Sarioglu envisions Cluster-Wells as being a routine part of the treatment process to determine what stage the cancer is at from a simple blood draw.

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